Role of class-II major histocompatibility complex (MHC)-antigen-positive donor leukocytes in transfusion-induced alloimmunization to donor class-I MHC antigens

It has been shown that peripheral-blood mononuclear leukocytes (MNL) are responsible for transfusion-induced alloimmunization to donor major histocompatability complex (MHC) antigens. However, it is not known which subset of MNL is responsible for this immune response. Because elimination of class-II MHC antigen-positive passenger leukocytes effectively prolongs the survival of allografts, it has been hypothesized that class-II positive MNL are responsible for immunizing transfusion recipients to donor MHC antigens. To test this hypothesis, two different approaches were used. First, we compared the alloantigenicity of BALB/c mice (H-2(d)) peripheral blood MNL before and after depletion of class-II positive cells. CBA mice (H-2(k)) were used as transfusion recipients. Antibody development to donor class-I H-2 antigens was determined by flow cytometry and enzyme-linked immunoassay. After four weekly transfusions of MNL depleted for class-II positive cells, only 25% of recipient mice developed antibodies to donor H-2(d) antigens. In contrast, all mice transfused with control MNL became immunized. Second, we studied the alloantigenicity of peripheral MNL from C57BL/6 mice (H-2(b)) with homozygous deficiency of class-II MHC molecules in H-2 disparate recipient mice. After transfusions with class-II MHC molecule-deficient MNL, 0% of BALB/c, 40% of C57BR, and 25% of CBA-recipient mice developed antibodies to donor H-2(b) antigen. All control recipient mice were immunized. The antibody activities of the controls were also higher than those in the treatment group who became immunized. Thus, our study shows that class-II MHC antigen-positive MNL play a significant role in transfusion-induced alloimmunization to donor class-I MHC antigens. The results also support the hypothesis that direct antigen presentation by donor class-II positive MNL to the immune system of transfusion recipients is critical for the initiation of humoral immune response to donor MHC antigens.     

Expansion of natural (NK1+) T cells that express alpha beta T cell receptors in transporters associated with antigen presentation-1 null and thymus leukemia antigen positive mice

Thymic selection of natural killer-1+ natural T cells that express alpha beta T cell receptors requires a conserved beta 2-microglobulin-associated molecule, presumably CD1d, displayed by CD4+8+ thymocytes. Here we demonstrate that positive selection of natural T cells occurs independent of transporters associated with antigen presentation-1 (TAP-1) function. Moreover, natural T cells in TAP-1o/o mice are numerically expanded. Several H-2 class Ib molecules function in a TAP-independent manner, suggesting that if expressed in TAP-1o/o thymocytes, they could play a role in natural T cell development. Of these class Ib molecules, H-2TL is expressed by TAP-1o/o thymocytes. Moreover, we find that thymi of TL+ mice congenic or transgenic for H-2T18 also have a numerically expanded natural T cell repertoire compared with TL- mice. This expansion, as in TAP-1o/o thymi, is evident in each of the limited T cell receptor V beta chains expressed by natural T cells, suggesting that TL and CD1d impact similar repertoires. Thus TL, in addition to CD1d, plays a role in natural T cell development.     

Tissue distribution, regulation and intracellular localization of murine CD1 molecules

CD1 molecules are MHC-unlinked class Ib molecules consisting of classical (human CD 1a-c) and non-classical subsets (human CD1d and murine CD1). The characterization of non-classical subsets of CD1 is limited due to the lack of reagents. In this study, we have generated two new anti-mouse CD1 monoclonal antibodies, 3H3 and 5C6, by immunization of hamsters with purified CD1 protein. These antibodies recognize CD1-transfected cells and have no reactivity to cells isolated from CD1-/- mice. Both antibodies precipitate the 52 kDa heavy chain and 12 kDa beta2m from thymocytes and splenocytes by radio-immunoprecipitation. Deglycosylation of CD1 reduces molecular mass of the heavy chain by 7.5 kDa, which can be detected by 3H3 but not 5C6. 3H3 and 5C6 detect surface CD1 expression on cells from the thymus, spleen, lymph node and bone marrow, but not on intestinal epithelial cells. Developmentally, CD1 is expressed on thymocytes prior to TCR rearrangement and remains constant throughout thymic development. CD1 is expressed early in the fetal liver (day 14) and remains expressed in hepatocytes postnatally. These data support evidence of a role for CD1 in the selection and/or expansion of NK1- T cells of both thymic origin and extrathymic origin. Unlike classical class I molecules, murine CD1 levels are not affected by IFN-gamma, but like human CD1b can be up-regulated by IL-4 and GM-CSF although only moderately. Similar to human CD1b, murine CD1 is found by immunofluorescence microscopy on the cell surface, and in various intracellular vesicles, including early and late endosomes. Localization in endocytic compartments indicates that murine CD1 may be capable of binding endocytosed antigens.     

Cross-reactions between mouse Ia and human HLA-D/DR antigens analyzed with monoclonal alloantibodies

Two mouse monoclonal anti-I-E/Ck alloantibodies (H7-8.26 and H10-81.10) directed against 2 distinct determinants of the specificity Ia-7 and 1 anti-I-Ak alloantibody (H8-15.9) directed against a public determinant common to the I-A subregion products of the H-2k, H-2b, H-2d, H-2q, and H-2ja haplotypes identified cross-reactive determinants on lymphoid cells from various mammalian species, including rat, dog, pig, cow, hamster, and guinea pig. In man, these antibodies detected nonpolymorphic determinants of DR antigens on B cell-enriched peripheral blood lymphocytes from 50 unrelated individuals. These cross-reactive DR determinants were also detected on lymphoblastoid B cell lines, on PHA-activated peripheral T lymphocytes, and on allospecific cytolytic T cell clones, but not on various DR-negative human T leukemia cell lines. Two chains of 29,000 and 35,000 daltons m.w., corresponding to DR antigens, were precipitated by H7-8.26 and H8-15.9 antibodies from radiolabeled membrane extracts of Raji cells. Competitive binding experiments indicated that the 3 mouse anti-Iak antibodies identified 3 distinct cross-reactive determinants on human cells. The results indicate that: a) The cross-reactivity described between mouse I-E/C gene products (Ia-7) and human DR antigen(s) involves, in fact, several distinct and topologically distant determinants. b) At least 1 determinant cross-reacting with DR can be identified on I-Ak gene products. c) The intriguing genetic problem of mouse MHC allotypic determinant(s) being nonpolymorphic in man cannot be simply explained by the deletion of an I-E alpha chain in some strains of mice.     

Monoclonal antibodies against Schistosoma mekongi surface tegumental antigens

Monoclonal antibodies were produced from naturally infected BALB/c mice. Thirteen hybridomas which were found to produce monoclonal antibodies against surface tegumental antigens of Schistosoma mekongi by ELISA assay were used in this study. The antigen specificities of hybridomas reactive with surface tegumental antigens were characterized and localized by immunoblotting analysis and Avidin-Biotin method. Of the 13 hybridomas, only three produced monoclonal antibodies to the single epitopes in the surface tegumental antigens. These epitopes (125 kDa, 97 kDa and 38 kDa) have been found to be the major antigenic components of the surface tegument of S. mekongi. The 38 kDa antigen was found to associate with the surface tegumental layers, the muscular layers lying just beneath the tegument, as well as in the gut surface. The 97 and 125 kDa antigens were detectable only in the surface tegumental area. The biochemical identity of these proteins or glycoproteins is unknown. However, these antigens have also been described in S. japonicum and S. mansoni.     

A role for Fas in negative selection of thymocytes in vivo

To seek information on the role of Fas in negative selection, we examined subsets of thymocytes from normal neonatal mice versus Fas-deficient lpr/lpr mice injected with graded doses of antigen. In normal mice, injection of 1-100 microg of staphylococcal enterotoxin B (SEB) induced clonal elimination of SEB-reactive Vbeta8+ cells at the level of the semi-mature population of HSAhi CD4+ 8- cells found in the thymic medulla; deletion of CD4+ 8+ cells was minimal. SEB injection also caused marked elimination of Vbeta8+ HSAhi CD4+ 8- thymocytes in lpr/lpr mice. Paradoxically, however, elimination of these cells in lpr/lpr mice was induced by low-to-moderate doses of SEB (相似文献   

Experimental infection of cattle with several Borrelia burgdorferi sensu lato strains; immunological heterogeneity of strains as revealed in serological tests

Twenty-three experimental cattle, mainly calves, were each inoculated 1-3 times with one of ten Finnish Borrelia burgdorferi sensu lato strains. All three genospecies were represented. Borreliae were administered mainly by both intravenous (about 10(6) to 10(9) spirochaetes) and intradermal (10(4)) routes, and on six occasions subcutaneously (10(3)) only. For infectivity control and comparison purposes mice and rabbits were inoculated simultaneously. Immune responses in cattle were monitored both with whole-cell sonicate enzyme-linked immunosorbent assay (IgG-ELISA) and indirect immunofluorescent assay (IgM-IgG-IFA). Five Finnish strains and the American strain B31 were used as antigens. No clinical signs of borreliosis were observed. Of the strains, 7/10 were interpreted by the immune responses to have caused relatively short-term subclinical infections of varying intensity. Borreliae could not be isolated from blood or other organ specimens of cattle. A rough estimate of the mean infectious dose in the conditions of experiments is 10(6) to 10(7) organisms. In conclusion, the overall result appears to argue a low susceptibility of cattle to clinical borreliosis, at least when infected by Finnish strains of the agent. Significant antigen-specific differences were observed both by ELISA and IFA in detection and quantification of immune responses. As a rule, the homologous antigen was found to be the most sensitive. Genospecies differences were mostly distinct. Antigens of two Borrelia garinii isolates proved practically equal in sensitivity, whereas major differences were displayed between two Borrelia afzelii antigens. In an IFA study, an American (B31) and a Finnish B. burgdorferi sensu stricto strain proved equally sensitive as antigens. In two relatively strong primary immune responses the antigen-specific measurement differences were such that diagnostically in a cross-sectional study only the homologous antigen or an antigen of the same genospecies would have been sufficiently sensitive to show a positive result.     

Tolerance induction by clonal deletion of CD4+8+ thymocytes in vitro does not require dedicated antigen-presenting cells

The cellular requirements of T cell tolerance induction in the thymus by clonal deletion was investigated by using an in vitro assay: thymocytes from mice expressing a transgenic TcR specific for lymphocytic choriomeningitis virus (LCMV) and H-2Db were co-cultured with various H-2b cell types as antigen-presenting cells in the presence of the antigenic LCMV peptide. The results revealed that all cell lines examined including embryonic and transformed fibroblasts, melanoma cells, cortical thymic epithelial cells, lymphomas and neuronal cells induced an antigen dose-dependent deletion of CD4+8+ thymocytes. Similarly, highly enriched accessory cell populations from thymus and spleen (macrophages, dendritic and cortical epithelial cells, i.e. thymic nurse cells) could induce antigen-specific depletion of immature CD4+8+ thymocytes. Depending on the cell type examined micromolar to picomolar concentration of LCMV peptide were required to induce deletion. The effectiveness of deletion by the different cell types did not correlate with their major histocompatibility class I expression level; it was, however, influenced by the presence of ICAM-1 adhesion molecules.     

Isotype-specific immune responses in murine experimental anisakiasis

A murine experimental model of anisakiasis has been developed in BALB/c and C57BL/10 mice orally inoculated with an Anisakis simplex living third stage larva (L3) in order to investigate isotype-specific immune responses against excretory-secretory (ES) products and crude extracts (CE) from L3. Specific antibody production showed similar patterns against both ES and CE antigens with higher levels against the latter. The dynamics of the production showed the earliest responses in BALB/c, in which antibodies were principally of the immunoglobulin (Ig)M isotype. Responses to the IgG1 subclass were mainly produced in the C57BL/10 strain. Levels of IgG2a were practically undetectable. With sera from C57BL/10 mice high levels of the IgG2b isotype were detected. A slight IgG3 response was only detected against the CE antigen in the C57BL/10 strain by the end of the experiment and IgA responses were very low. Humoral responses against A. simplex antigens are different depending on individual characteristics and thymus-independent epitopes might be represented into A. simplex antigens and their stimuli could be different regarding the murine strain used.     

Effects of cytokines and glucocorticoids on endogenous class II MHC antigen expression by activated rat CD4+ T cells. Mature CD4+ CD8- thymocytes are phenotypically heterogeneous on activation

By the use of mixed leukocyte cultures it was shown that a population of allogeneically activated rat T cells synthesize and express class II MHC antigens, in confirmation of other studies. Compatible with the finding that the MHC molecules detected on these cells were of T cell origin rather than passively acquired, it was found that mRNA for class II transactivator could readily be detected in the T cells stimulated in these cultures. In contrast there was no evidence that mouse T cells synthesized class II MHC antigens. The size of the population of activated rat T cells expressing class II MHC antigens was affected by the presence of IL-4 and glucocorticoids in the activating cultures. However, whereas IL-4 increased the frequency of thymocytes and peripheral T cells expressing class II antigens in culture, glucocorticoids diminished this frequency. The expression of class II MHC antigens by allogeneically activated thymocytes demonstrated a novel heterogeneity amongst mature CD4+ CD8- thymocytes that could not readily be accounted for in terms of differences in maturity of the cells, in the affinity of the TCR for the stimulating ligands or in the stage in the cell cycle. The data suggest that CD4+ single-positive thymocytes do not constitute a homogeneous population differing only in TCR clonotypes.     

A novel subset of adult gamma delta thymocytes that secretes a distinct pattern of cytokines and expresses a very restricted T cell receptor repertoire

We have characterized the function, phenotype, ontogenic development, and T cell receptor (TCR) repertoire of a subpopulation of gamma delta thymocytes, initially defined by expressing low levels of Thy-1, that represents around 5% and 30% of total gamma delta thymocytes in adult C57BL/6 and DBA/2 mice, respectively. Activation of FACS-sorted Thy-1dull gamma delta thymocytes from DBA/2 mice with anti-gamma delta monoclonal antibodies in the presence of interleukin-2 (IL-2) results in the secretion of high levels of several cytokines, including interferon-gamma (IFN-gamma), IL-4, IL-10, and IL-3. In contrast, only IFN-gamma was detected in parallel cultures of Thy-1bright gamma delta thymocytes. Virtually all Thy-1dull gamma delta thymocytes express high levels of CD44 and low levels of the heat-stable antigen and CD62 ligand, while around half of them express the NK1.1 marker. Thy-1dull gamma delta thymocytes are barely detectable in newborn animals, and their representation increases considerably during the first 2 weeks of postnatal life. The majority of Thy-1dull gamma delta thymocytes from DBA/2 mice express TCR encoded by the V gamma 1 gene and a novel V delta 6 gene named V delta 6.4. Sequence analysis of these functionally rearranged gamma and delta genes revealed highly restricted V delta-D delta-J delta junctions, and somewhat more diverse V gamma-J gamma junctions. We conclude that Thy-1dull gamma delta thymocytes exhibit properties that are equivalent to those of natural killer TCR alpha beta T cells. Both cell populations produce the same distinct pattern of cytokines upon activation, share a number of phenotypic markers originally defined for activated or memory T cells, display similar postnatal kinetics of appearance in the thymus and express a very restricted TCR repertoire.     

Intestinal metaplasia with adherent Helicobacter pylori: a hybrid epithelium with both gastric and intestinal features

Helicobacter pylori seem to avoid areas of intestinal metaplasia in the gastric mucosa, but attachment of these bacteria to epithelium with the appearance of incomplete intestinal metaplasia has been documented. To characterize the nature of the epithelium to which H pylori was attached, we carried out an immunohistochemical study using monoclonal antibodies against gastric surface mucous cell mucins (M1), blood group-related carbohydrates antigens (Le(a), sialyl Le(a), Le(b), type 1H, and type 2H) and sialyl Tn antigen. The results of this study suggest that these areas of H pylori attachment represent a hybrid epithelium whose cells share characteristics of both gastric surface mucous cells and intestinal metaplastic cells. Whether all areas of incomplete intestinal metaplasia represent an intermediate stage between the normal gastric epithelium and the fully developed complete type of metaplasia remains to be determined.     

Long-term lipid-based total parenteral nutrition activates mononuclear cells and modulates membrane lipid composition in pigs

This study aims to assess the possible strain-dependent variations in detection of Toxoplasma antigens and antibodies. The virulent RH strain or avirulent Beverley strain of T. gondii were injected into mice, intraperitoneally, and their antigens, antibodies and parasites were identified from the blood or tissues; liver, brain and spleen by ELISA, Western blot and PCR. In mice infected with RH strain, circulating antigens and parasitemia were first detected from 2 days after infection, and Toxoplasma DNA were found in the blood, liver, brain and spleen from 3 days after infection. It was impossible to detect specific IgM and IgG antibodies to T. gondii, and any specific band was not found by Western blot. In mice infected with Beverley strain, circulating antigens were detected between day 10 and day 35. The Toxoplasma DNA was found in the blood and liver from day 15 until day 60, and in the brain from day 20. But Toxoplasma DNA in the spleen were mainly detected between day 10 and day 30. The IgM antibodies were first appeared on day 10 post-infection, and were noted obviously increased between day 15 and 25. The IgG antibodies were first detected on day 15, and showed progressively increased titers. The antibody binding bands were specific according to infection period. Sera from mice infected with Beverley strain reacted mainly with the antigen of 27.5-kDa and 32.5-kDa. In conclusion, mice infected with RH strain revealed Toxoplasma antigens strongly, but not antibodies. However, mice infected with Beverley strain revealed both the Toxoplasma antigens and antibodies. The present results showed that immune responses are different between avirulent and virulent T. gondii.     

Distribution of blood-group-related carbohydrate antigens on oral endothelial cells

Recent studies indicate that carbohydrate structures are involved in various endothelial functions such as inflammatory processes, adhesion of metastatic cells to endothelium and endothelial differentiation. In this paper we report the endothelial expression of various blood-group-related carbohydrate structures in normal oral mucosa using 15 different monoclonal antibodies reacting with type 1, 2 or 3 carbohydrate chains. Twenty biopsies, including normal oral mucosa, from secretor individuals comprised nine blood group O, nine A, one B and one AB. Endothelial staining was compared with epithelial staining in the same biopsies. Five blood-group-related carbohydrate antigens were detected on endothelial cells. The H type 2 antigen, which is the precursor of A, B and AB antigens, has previously been believed to be a universal marker for endothelial cells. All blood group O individuals (n = 9) showed strong H antigen staining in the endothelium of most vessels. However, of blood group A, B and AB individuals (n = 11), four showed heterogenous H antigen staining. In addition, we found that six out of ten blood group A or AB individuals, who expressed A or A and B antigens on spinous squamous cells and glandular epithelium, showed either heterogenous or no staining for these structures on their endothelial cells. It is concluded that there are differences between the biosynthesis of blood-group-related carbohydrate antigens in oral endothelium and epithelium.     

An Eikenella corrodens toxin detected by plaque toxin-neutralizing monoclonal antibodies

Bacterial plaque from the gingival region of teeth contains cytotoxic agents which lyse undifferentiated human HL60 cells. A small panel of monoclonal antibodies (MAbs) was found to abrogate much of this activity and to detect antigens in certain strains of Streptococcus mitis and Eikenella corrodens. The aim of this study was to determine whether these bacterial antigens might be involved in HL60 cells cytolysis. Saline extracts were obtained by homogenizing washed, stationary-phase cells in 65 mM NaCl with a tight-fitting Potter-Elvehjem homogenizer. The extracts of E. corrodens were toxic to HL60 cells, whereas similar extracts of S. mitis were nontoxic. Adding plaque toxin-neutralizing MAb 3hE5 blocked the toxic effect of E. corrodens extract S. mitis extracts contained a single, strongly reactive antigen of 140 kDa (s140K antigen) detected on Western blots (immunoblots) by three MAbs from the panel. Rabbit antibodies raised to this antigen excised from the gel (anti-s140K serum) detected larger antigens in addition to s140K. E. corrodens extracts contained a number of antigens detected by the MAbs. Immunoglobulin G (IgG) was purified from anti-s140K serum by passage through DE52 cellulose. A 100-fold excess (by weight) of the purified IgG to E. corrodens protein specifically cross-precipitated an 80-kDa antigen plus a nonantigenic 16-kDa protein, presumably attached noncovalently. The remaining supernatant fraction had no toxic activity. A similar ratio of control IgG (from nonimmunized rabbits) did not precipitate these proteins, and the supernatant fraction had the same activity as the extract not treated with IgG. The proteins of 80 and 16 kDa were also detected in the anti-s140K immunoprecipitate by rabbit IgG antibodies to E. corrodens whole cells. The 80-kDa antigen, alone or complexed with the 16-kDa protein, may be involved in mediating the toxic activity in E. corrodens and plaque extracts.     

Activity of placental glutathione peroxidase and superoxide dismutase in cows with and without retained fetal membranes

We recently reported that there are two different virulence-associated antigens correlated with virulence levels in Rhodococcus equi isolates from AIDS patients: virulent R. equi that kills mice with 10(6) cells expresses 15- to 17-kDa antigens and intermediately virulent R. equi that kills mice with 10(7) cells expresses a 20-kDa antigen. Environmental parameters were evaluated for their effects on the expression of these virulence-associated antigens in virulent R. equi strains by immunoblotting using monoclonal antibodies in this study. Expression of these two virulence-associated antigens of R. equi was regulated by pH and temperature; the antigens were produced maximally when the isolates were grown at 38 C and pH 6.5, but were not produced when grown at 38 C and pH 8, nor at temperatures below 30 C. The 20-kDa antigen was found to be located on the cell surface, as were the 15- to 17-kDa antigens, and showed susceptibility to proteolysis by trypsin. These results indicate that expression of the virulence-associated antigens of R. equi is dependent on the environmental conditions.     

Kinetics study and characterisation of target excreted/secreted antigens of immunoglobulin G, M, A and E antibodies from mice infected with different strains of Toxoplasma gondii

A kinetics study and characterisation of target excreted/secreted antigens of immunoglobulin (Ig) G, M, A and E antibodies were realised by Western blotting with immune sera of mice inoculated with three strains of Toxoplasma gondii: RH, C56 and S3. IgG antibodies of the immune sera recognised the major proteins of the three excreted/secreted antigen preparations with molecular masses of 30, 45, 63 and 77 kDa. IgM antibodies recognised proteins revealed by IgG antibodies but with variable intensities; some proteins were revealed during a short period. IgA antibodies did not recognise the 35-kDa antigen or the antigens inferior to 28 kDa. The RH excreted/secreted antigens were revealed with the highest intensity. The IgE antibodies were briefly detected in trace amounts during period from the 20th to the 35th day. The RH strain with its excreted/secreted antigens had the best antigenicity and is a good model for immunoprotection studies.     

Cell-mediated immunity against particulate and solubilized tumor-associated antigens of murine plasmacytomas detected by macrophage migration inhibition assays

Cell-mediated immunity (CMI), as detected by the agarose microdroplet macrophage migration inhibition (MMI) assay, was investigated using peritoneal exudate cells (PEC) of BALB/c mice and several crude membrane (CM) and solubilized preparations of murine plasmacytomas. The MMI assay was quite sensitive and detected inhibition of macrophage migration as low as picogram quantities of CM, NP40 detergent- and papainsolubilized preparations (CS) of ADJ-PC5 and LPC-1 plasmacytomas. The data were highly reproducible from one experiment to the next with the same or different lots of the CM or solubilized extracts. Specificity studies demonstrated that ADJ-PC5 and LPC-1 plasmacytomas expressed cross-reactive tumor-associated antigens (TAA) as detected by MMI and confirmed by tumor challenge and Winn neutralization experiments. No cross-reactivity was observed with similar extracts prepared from an unrelated syngeneic simian virus 40 (SV40)-induced sarcoma. The inhibition of macrophage migration observed was mediated by culture supernatants generated from the mixture of plasmacytoma-immune spleen cells with antigens and then assayed in an indirect MMI assay on normal PEC. The agarose microdroplet MMI assay appeared to be a rapid and sensitive method to measure TAA recognition and to monitor TAA isolation and solubilization with minimum numbers of immune cells.     

Isotype responses to candidate vaccine antigens in protective sera obtained from mice vaccinated with irradiated cercariae of Schistosoma mansoni

In experimental schistosomiasis, sera of mice multiply vaccinated with radiation-attenuated cercariae of Schistosoma mansoni passively transfer resistance against cercarial challenge to naive mice. To further characterize these sera, we tested their protective capacities in two mouse strains (C57BL/6J and CBA/J) and compared the antigen-specific isotype compositions of the different protective sera by means of the enzyme-linked immunosorbent assay. By using an array of purified schistosomal antigens, the patterns of antibody titers and isotypes differed for each experimental group and antigen. In the most-protective C57BL/6J sera, high levels of immunoglobulin G1 (IgG1), IgG2a, and IgG2b bound to heat shock protein 70 and the integral membrane protein Sm23, whereas recognition of these antigens by less-protective CBA/J sera was lower. Glutathione S-transferase (GST) was recognized predominantly by IgM antibodies of all vaccinated groups, and a significant portion of this response was directed against carbohydrate epitopes. Antibodies specific for triosephosphate isomerase, paramyosin, and Sm32 (hemoglobinase) were present in less-protective sera and thus seem less relevant for passive transfer of resistance. The results of this study suggest a contribution of IgG antibodies specific for heat shock protein 70 and Sm23, and possibly a contribution of GST-specific IgM antibodies, to the protective effect of sera from C57BL/6J mice vaccinated with irradiated cercariae.     

Regulation of the immune system by synthetic polynucleotides. VI. Amplification of the immune response in young and aging mice

Model systems for study of the action of adjuvants in immunodeficient states were developed in 10- to 14-day-old BALB/aj mice and aging BALB/aj mice (12 to 16 months). With sheep red blood cells as antigen polyadenylicpolyuridylic acid complexes (poly A:U) were found to be stimulatory in both the neonatal and aging mice. The effect of poly A:U was similar to that seen when 5 X 10(6) thymocytes from immunologically mature mice were given with antigen. Cell-free supernatant fluids induced by incubation of poly A:U with thymocytes likewise were capable of restoring the number of antibody-forming cells to normalcy in aging mice.