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M Zauderer

Publications and source records attributed to M Zauderer.

29 records · Page 2Linked to original sources
PubMed1986

Gamma gene rearrangement and expression in autoreactive helper T cells.

gamma gene rearrangements similar to those described for cytotoxic T cell lines are found in L3T4+, autoreactive, or KLH-specific cloned helper T cell lines. High levels of gamma RNA transcripts were, in addition, detected in four out of five L3T4+, class II MHC-specific, autoreactive T cell clones, and in at least one of three KLH-specific, class II MHC-restricted clones. This contrasts with previously reported (9) expression of gamma RNA in only 1 of 11 antigen-specific helper T cell lines.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1985

Origin and specificity of autoreactive T cells in antigen-induced populations.

We have characterized the major histocompatibility complex (MHC) specificity of autoreactive T cell clones arising from diverse donors after immunization with different antigens. The MHC fine specificity of autoreactive T cells for unique F1 hybrid determinants of BALB.K X BALB.B F1, and for the mutant I-Ab determinants of the B6.C-H-2bm12 (bm 12) strain is similar to that previously described for antigen-specific T cells. We find, furthermore, that the MHC specificity of autoreactive T cell clones selected from primed populations grown in the absence of Con A-stimulated supernatant factors reflects the predominant MHC restriction specificity of T cells specific for the immunogen. Thus, I-E subregion-specific autoreactive T cells are detected at a much higher frequency after immunization with the I-E-restricted antigen, GL (terpolymer of glutamic acid, lysine, and phenylalanine), than with the predominantly I-A-restricted antigen, keyhole limpet hemocyanin (KLH). These experiments strongly suggest that some autoreactive T cells are derived from antigen-stimulated precursors. This result contrasts with that obtained when autoreactive T cells are selected in bulk cultures, or in the presence of exogenous T cell factors. We conclude that, under optimal conditions, most autoreactive T cells are recruited from a relatively stable pool of predominantly I-A-specific precursors. Autoreactive precursors in this pool might themselves derive from previous antigenic stimulation, or be of independent origin.

Animals↗
PubMed1984

Helper functions of antigen-induced specific and autoreactive T cell colonies.

Helper T cells have been distinguished on the basis of whether they provide carrier-specific or nonspecific helper functions. In previous experiments we determined that the predominant class of helper T cell in populations of primed lymph node cells is a nonspecific helper T cell unable to provide carrier-specific signals. Initial induction of nonspecific helper T cells in vitro requires restimulation with the immunogen. This suggested that such T cells may express antigen-specific receptors. In this case they would constitute a unique subpopulation distinct from T cells with identical antigen-specificity that are able to provide carrier-specific help. Alternatively, the requirement for antigen restimulation might reflect a role for antigen-specific T cells in the recruitment of T cells with unrelated specificity. To distinguish between these possibilities we have characterized the specificity and function of helper T cell colonies selected from primed lymph node cells. We report here isolation of autoreactive as well as antigen-specific helper T cells. All antigen-specific T cell colonies provide carrier-specific help in the presence of the homologous hapten-carrier conjugate. Only autoreactive T cells are limited to providing nonspecific helper function. Although selection of autoreactive T cells is initially dependent on antigen restimulation in vitro, activation of an established autoreactive T cell line requires restimulation with MHC-syngeneic spleen cells but does not require restimulation with either the immunogen or fetal calf serum. These results suggest that nonspecific helper T cells induced in the course of a normal immune response to randomly chosen foreign antigens are autoreactive. Such T cells may serve to enhance proliferation and maturation to immunoglobulin secretion of B cells activated by limiting numbers of carrier-specific helper T cells. The demonstration of large numbers of precursors to MHC-specific autoreactive T cells in antigen-primed populations raises important issues concerning regulation of the expansion of autoreactive T cells in vivo.

Animals↗
PubMed1982

Functionally distinct helper T cells enriched under different culture conditions cooperate with different B cells.

Helper T cells selected from KLH-primed lymph node cells under different in vitro conditions were analyzed for the ability to cooperate in secondary hapten-specific antibody responses. It is shown that carrier-specific, MHC-restricted helper T cells selected in low-density cultures cooperate with equal efficiency in either PC-specific or DNP-specific responses. In the presence of both PC-specific and DNP-specific B precursors, however, such T cells are limited to participate in only one helper event in vitro. In contrast, the predominant helper T cell in a second population maintained in high-density lymph node cultures cooperates, presumably through a soluble factor, with multiple B precursors. These properties correspond to those previously described for specific and nonspecific effector functions. The experiments reported here further demonstrate that different B cells respond in vitro to carrier-specific and nonspecific helper signals.

Animals↗
PubMed1981

Clonal analysis of F1 hybrid helper T cells. I-A subregion-encoded hybrid determinants restrict the activity of keyhole limpet hemocyanin-specific helper T cells.

Clonal expansion of isolated precursors to helper T cells was induced in limiting dilution cultures of keyhole limpet hemocyanin (KLH)-primed F1 hybrid lymph node cells. Progeny of each isolated precursor was tested for helper activity by transfer to independent cultures with hapten-primed B cells of either parental or F1 hybrid origin. The major histocompatibility complex (MHC) restriction specificity of each F1 hybrid helper T clone was determined. To assess the contribution of I-A and I-E subregion-encoded genes to the expression of these restriction elements, helper T cell cultures derived from F1 hybrids between strains with recombinant H-2 haplotypes were analyzed. Parental and unique F1 hybrid MHC determinants that are encoded entirely within the I-A subregion were found to restrict the activity of KLH-specific helper T cells.

Animals↗
PubMed1980

Clonal analysis of F1 hybrid helper T cells restricted to parental or F1 hybrid major histocompatibility determinants.

Antigen-specific major histocompatibility complex (MHC)-restricted helper T cell precursors were induced to proliferate in cultures of keyhole limpet hemocyanin-primed lymph node cells. Clones of F1 hybrid helper T cells were isolated in limiting-dilution cultures. Each positive culture at a limiting-dilution of lymph node cells gave rise to > 10 helper T cells with a single MHC-restricted specificity. This made it possible to independently assay specific helper activity of isolated clones in secondary cultures with B cells of diverse origin. Different clones with helper activity restricted to either parental or unique F1 hybrid MHC determinants were found to occur at approximately equal frequency. The results are discussed in relation to hybrid Ia specificities and dual-complementing MHC-linked Ir genes.

Animals↗
PubMedDate not supplied

Specific T-cell response to a Pneumocystis carinii surface glycoprotein (gp120).

Pneumocystis carinii gp120 can elicit a specific T-cell proliferative response in mice after immunization with a gp120 preparation or with a crude P. carinii homogenate. It can also elicit a proliferative response from SCID mice after recovery from natural infection with P. carinii, implicating this glycoprotein as an important antigen in the host's response to P. carinii infection.

Animals↗