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R J Hodes

Publications and source records attributed to R J Hodes.

At least 145 records · Page 8Linked to original sources
PubMed1982

T cell regulation of B cell activation. T cells independently regulate the responses mediated by distinct B cell subpopulations.

The present studies have been carried out to characterize the regulatory influences acting upon defined pathways of T cell-dependent B cell activation. In these studies, it was demonstrated that high concentrations of free carrier strongly inhibited the MHC-restricted in vitro T cell-dependent antibody responses of primed Lyb-5- B cells to the corresponding carrier-hapten conjugate. In contrast, these same concentrations of free carrier failed to inhibit the T cell dependent responses of Lyb-5+ B cells to the same antigen. The inhibition of Lyb-5- B cell responses by free carrier was shown to result from active suppression mediated by carrier-specific primed Lyt-1+2- T cells and to require the additional participation of unprimed Lyt-1-2+ T cells. The activation of this suppression was antigen-specific, but suppression once activated was antigen nonspecific in its effect. These findings thus demonstrate that distinct pathways of B cell activation can be independently regulated by T suppressor network influences, and that these pathways therefore constitute potentially independent components of the immune response to a given antigenic stimulus.

Animals↗
PubMed1982

Modification of T cell antinuclease idiotype expression by in vivo administration of anti-idiotype.

Immunization of BALB/c mice with nuclease leads to the production of anti-nuclease antibodies bearing a set of cross-reactive idiotypes (Id) distinct from those produced by B10.D2 mice after similar immunization. In both strains, such immunization with nuclease also leads to the production of splenic T helper cells (TH), which provide nuclease-specific help in an in vitro plaque-forming cell response to nuclease-TNP. Pig anti-(BALB/c antinuclease) anti-idiotypic antibodies (pig anti-BALB/c Id) react only with TH of nuclease-primed BALB/c and not with B10.D2 animals. After administration of pig anti-BALB/c Id in complete Freund's adjuvant to BALB/c and B10.D2 mice, Id-bearing nonantigen-binding molecules were induced in both strains. Such treatment also resulted in the induction of nuclease-specific splenic TH cells in both strains. BALB/c TH cells induced by anti-Id, like the majority of nuclease-primed BALB/c TH cells, bore BALB/c Id, as shown by their functional elimination with anti-Id plus complement. B10.D2 TH cells induced by anti-Id, unlike TH cells from nuclease-primed B10.D2 mice, also bore BALB/c idiotypic determinants by the same criterion. Thus, it appears that one can manipulate the expression of Id on serum immunoglobulins and on antigen-specific TH cells by administration of exogenous anti-Id reagents. These results have implications both for network interactions in the immune response and for the genetic basis of Igh-C linked Id expression.

Animals↗
PubMed1982

Self recognition in allogeneic thymic chimeras. Self recognition by T helper cells from thymus-engrafted nude mice is restricted to the thymic H-2 haplotype.

To examine the possibility that the thymus determines the I region-restricted self-recognition repertoire expressed by T helper (TH) cells, thymic chimeras were constructed by transplanting allogeneic neonatal thymic lobes into congenitally athymic nude mice. Spleen TH cells from the thymic chimeras were themselves of nude host origin but only cooperated with B+ accessory cells of the thymic haplotype for primary in vitro responses to sheep erythrocytes and trinitrophenyl conjugate of keyhole limpet hemocyanin. Thus, these experiments demonstrate that the self-recognition repertoire expressed by TH cells is determined by the H-2 phenotype of the intrathymic environment in which the TH cells had differentiated.

Animals↗
PubMed1982

The expression and functional involvement of nuclease- specific idiotype on nuclease-primed helper T cells.

The expression and functional significance of idiotypic determinants on antigen-specific helper T (Th) cell populations for responses to Staphylococcal nuclease (Nase) were evaluated in an in vitro antibody response system. Trinitrophenyl (TNP)- specific plaque-forming cell responses to TNP-conjugates of Nase (TNP-Nase) were shown to require the cooperation of Nase-primed Th cells as well as unprimed B and accessory cells. The expression on these antigen-primed Th cells of idiotypic determinants cross-reactive with those on anti-Nase antibodies was demonstrated by the specific elimination of Th cells for TNP-Nase by treatment with affinity-purified anti-idiotypic antibodies plus complement. The susceptibility of Nase-primed Th cells to elimination by such treatment was specific in that anti-idiotypic antibodies affected Th cells only from strains normally expressing the same (or a cross-reactive) idiotype on anti-Nase antibodies. A functional role of the idiotypes expressed on Nase-primed Th cells was suggested by the fact that anti-idiotypic antibody present throughout the period of culture, in the absence of complement, suppressed responses to TNP-Nase in an antigen- and strain-specific manner. It was further shown, by cell mixing experiments, that this inhibition appeared to occur at the level of the Th cells and was not dependent on the strain of origin of the B cells. Thus, antigen-specific Nase-primed Th cells express strain-specific idiotypic determinants cross-reactive with, or identical to, those of anti-Nase antibodies. These cell surface idiotypic determinants appear to be functionally involved in the activity of Th cells for the induction of antibody responses to TNP-Nase in vitro.

Animals↗
PubMed1982

Generation of the alloreactive T-cell repertoire: interaction of T-cell genotype and maturation environment.

The influences of the T-cell genotype and the T-cell maturation environment on generation of the T-cell alloreactive repertoire were evaluated in cytotoxic T-lymphocyte responses to Kb mutant determinants expressed by the strains B6. C-H-2bm1 and B6-H2-bm6. By constructing bone marrow chimeras using either H-2b of H-2d mice as the source of donor cells and either H-2d or H-2b irradiated mice as recipients, it was first determined whether the T-cell major histocompatibility complex genotype alone determines the alloreactive repertoire. The results of such experiments indicated that H-2b T cells that have matured in a normal H-2b environment (C57BL/6N, C57BL/10Sn) or H-2d T cells that have matured in a chimeric H-2b environment (B10.D2 leads to C57BL/10Sn) are responsive to Kbm1 and Kbm6 determinants while H-2b T cells that have matured in an H-2d chimeric environment (C57BL/10Sn leads to B10.D2) have a diminished responsiveness to H-2bm1 and are completely unresponsive to H-2bm6. These findings showed that T-cell genotype alone does not determine the alloreactive repertoire to mutant Kbm1 and Kbm6 determinants and suggested that the T-cell maturation environment plays a critical role in this process. Further studies were carried out to determine whether the T-cell maturation environment alone determines this repertoire, such that maturation in an H-2b but not in an H-2d environment is both necessary and sufficient to generate reactivity to Kbm6. Experiments in which either H-2d responder populations neonatally made tolerant to H-2b or unlabeled target blocking of normal H-2d responders were used provided evidence that T cells specific for Kbm6 mutant determinants are present in the repertoire of H-2d T cells that have matured in an H-2d environment. These findings suggest that the alloreactive T-cell repertoire is not determined by the T-cell major histocompatibility complex genotype alone or by the T-cell maturation environment alone but rather than it is the product of unique interactions between the two.

Animals↗
PubMed1982

Role of the major histocompatibility complex in T cell activation of B cell subpopulations: antigen-specific and H-2-restricted monoclonal TH cells activate Lyb-5+ B cells through an antigen-nonspecific and H-2-unrestricted effector pathway.

Monoclonal T helper (TH) cell populations were employed to study the mechanism of activation of the Lyb-5+ B cell subpopulation in T cell-dependent antibody responses in vitro. It was demonstrated that monoclonal T cell populations were sufficient to help rigorously T-depleted unprimed (B + accessory) cells for direct plaque-forming cell responses to trinitrophenyl- (TNP) conjugated keyhole limpet hemocyanin (KLH). The activation of several lines of cloned (H-2b X H-2k)F1 TH cells was antigen (KLH) specific and H-2 restricted. Individual clones were restricted to H -2b, H-2k, or unique (H-2b X H-2k)F1 encoded determinants. Under the experimental conditions employed, responses mediated by cloned TH cells were found to result in the activation of the Lyb-5+ B cell subpopulation. The activation of Lyb-5+ B cells by cloned TH cells did not require covalent linkage of carrier and hapten, and responses could be stimulated in the presence of free KLH plus TNP conjugated to an irrelevant carrier. The H-2 restriction of TH cell function was shown to reflect a requirement for T cell recognition of determinants expressed by accessory cells, whereas no requirement existed for restricted T cell recognition of B cells. These findings suggest that the help provided by monoclonal TH cells, once activated, was both antigen nonspecific and H-2 unrestricted. Consistent with this interpretation, it was found that the supernatant of antigen-stimulated TH cells provided antigen-nonspecific help to T-depleted spleen cells. Thus, these results demonstrate that the activation of Lyb-5+ B cells by antigen-specific and H-2-restricted monoclonal TH cell populations is itself antigen nonspecific and H-2 unrestricted.

Animals↗
PubMed1981

Role of the major histocompatibility complex in T cell activation of B cell subpopulations. Major histocompatibility complex-restricted and -unrestricted B cell responses are mediated by distinct B cell subpopulations.

The present study has evaluated the identity of the B cell subpopulations participating in T dependent antibody responses that differ in their requirements for major histocompatibility complex-restricted T cell recognition. In vitro responses of keyhole limpet hemocyanin (KLH)-primed T cells and trinitrophenyl (TNP)-primed B cells were studied to both low and high concentrations of the antigen TNP-KLH. It was first demonstrated that for responses to low concentrations of TNP-KLH, (A x B)F(1) {arrow} parent(A) chimeric helper T cells were restricted in their ability to recognize parent(A) but not parent(B) H-2 determinants expressed by both B cells and antigen-presenting cells (APC). In contrast, at higher antigen concentrations, helper T cells were not restricted in their interaction with B cells. It was then determined whether these observed differences in T cell recognition resulted from the activation of distinct B cell subpopulations with different activation requirements. At low concentrations of TNP-KLH it was demonstrated that Lyb-5(-) B cells were activated, and that it was thus the activation of the Lyb-5(-) subpopulation that required T cell recognition of B cell H-2 under these conditions. In contrast, responses to high concentration of antigen required the participation of Lyb-5(+) B cells, and these Lyb-5(+) B cells were activated by a pathway that required H-2- restricted T cell interaction with APC, but not with B cells. The findings presented here have demonstrated that Lyb-5(-) and Lyb-5(+) B cells constitute B cell subpopulations that differ significantly in their activation requirements for T cell-dependent antibody responses to TNP-KLH. In so doing, these findings have established that the function of genetic restrictions in immune response regulation is critically dependent upon the activation pathways employed by functionally distinct subpopulations of B, as well as T, lymphocytes.

Animals↗
PubMed1981

Role of the major histocompatibility complex in T cell activation of B cell subpopulations Lyb-5+ and Lyb-5- B cell subpopulations differ in their requirement for major histocompatibility complex-restricted T cell recognition.

This report has examined the requirements for T helper (T(H)) cell recognition of major histocompatibility complex (MHC) determinants expressed by B cells for the activation of unprimed Lyb-5(+) and Lyb-5(-) B cell subpopulations . The generation of primary T(H) cell-dependent plaque-forming cell responses in vitro microculture required the presence of Lyb-5(+) B cells because B cell populations that were deprived, either genetically or serologically, of the Lyb-5(+) subpopulation were not activated in these responses. Cell-mixing experiments in which A X B {arrow} A chimeric T(H) cells were mixed with purified populations of parental accessory cells and parental B cells demonstrated that the in vitro activation of Lyb-5(+) B cells did not require T(H) cell recognition of B cell MHC determinants, although it did require T(H) cell recognition of accessory cell MHC determinants . In contrast to the failure of Lyb-5(-) B cells to be activated in primary T(H) cell-dependent responses in vitro microculture, isolated populations of Lyb-5(-) B cells were triggered by T(H) cells in vivo in short-term adoptive transfer experiments . By the use of A X B {arrow} A chimeric T(H) cells and parental strain B adoptive hosts, it was possible in vivo to distinguish genetically restricted T(H) cell recognition of B cells from genetically restricted T(H) cell recognition of accessory cells. Similar to the results obtained in vitro, the activation in vivo of unfractionated (Lyb-5(+) plus Lyb-5(-)) B cell populations did not require T(H) cell recognition of B cell MHC determinants . In contrast, in the same in vivo responses activation of isolated populations of Lyb-5(-) B cells did require T(H) cell recognition of B cell MHC determinants. The most straightforward interpretation of these experiments is that T(H) cell recognition of B cell MHC determinants is required for the activation of Lyb-5(-) B cells but is not required for the activation of Lyb-5(+) B cells . To better understand why T(H) cell activation of one B cell subpopulation is genetically restricted, whereas activation of another subpopulation is not, the response of Lyb-5(+) and Lyb-5(-) B cells to the soluble activating factors present in concanavalin A-induced spleen cell supernates (Con A SN) was examined. It was observed that Lyb-5(-) B cells, as opposed to Lyb-5(+) B cells, were unable to respond in microculture to the nonspecific T(H) cell- activating factors present in Con A SN, even though they were able to nonspecifically respond under the same conditions to trinitrophenyllipopolysaccharide. It was observed that the ability of B cell subpopulations to respond to nonspecific soluble T cell factors paralleled their ability to be activated by T(H) cells in a genetically unrestricted manner. Thus, the present experiments demonstrate that activation by T(H) cells of Lyb-5(-) B cells is MHC restricted, whereas activation of Lyb-5(+) B cells is not. These experiments suggest that one possible explanation for such differences is that activation of Lyb-5(+) B cells does not require direct interaction with T(H) cells because they can be activated by soluble activation signals that T(H) cells secrete.

Antibody-Producing Cells↗
PubMed1981

Induction of idiotype-bearing, nuclease-specific helper T cells by in vivo treatment with anti-idiotype.

Treatment of BALB/c mice with purified pig anti-(BALB/c anti-nuclease) anti-idiotypic antibodies has been found to induce the appearance of idiotype-bearing immunoglobulins (Id') in the serum of these mice in the absence of detectable antigen binding activity. This phenomenon appeared to require T cells in the hosts because no Id' was detected in the serum of nude mice similarly treated. Furthermore, the spleens of BALB/c mice treated with anti-idiotype were found to contain helper T cells capable of providing help in an in vitro plaque-forming cell response to trinitrophenyl-nuclease equivalent to that provided by helper T cells from the spleens of nuclease-primed animals. Helper T cells from both anti-idiotype-treated and nuclease-treated animals were found to be antigen-specific and to be similarly susceptible to elimination by treatment with anti-idiotype plus complement. Therefore, treatment with both antigen and anti-idiotype appeared to prime similar populations of antigen-specific helper T cells, while having different effects on the induction of antibody. These findings are consistent with the network theory of receptor interactions in the immune response, and may provide a means for studying individual cell populations involved in such interactions.

Animals↗
PubMed1981

Self recognition in allogeneic radiation bone marrow chimeras. A radiation-resistant host element dictates the self specificity and immune response gene phenotype of T-helper cells.

The specificity of the self-recognition repertoire in fully allogeneic (A {arrow} B), semiallogeneic (A {arrow} A x B and A x B {arrow} A), and double donor (A + B {arrow} A) radiation bone marrow chimeras was assessed by the ability of their spleen cells to generate in vitro primary plaque-forming cell (PFC) responses to trinitrophenyl- keyhole limpet hemocyanin. In contrast to spleen cells from semiallogeneic and double donor chimeras, intact spleen cells from fully allogeneic BI0 {arrow} B10.A and B10.A {arrow} B10 chimeras were not capable of generating responses to trinitrophenyl (TNP)-keyhole limpet hemocyanin. However, cultures containing a mixture of both B10 {arrow} B10.A and B10.A {arrow} B10 spleen cells did respond, demonstrating that all the cell populations required for the in vitro generation of T-dependent PFC responses were able to differentiate into functional competence in a fully allogeneic major histocompatibility complex (MHC) environment. The self recognition repertoire of T-helper cells from fully allogeneic A {arrow} B chimeras was determined to be specific for the recognition of host, not donor, MHC determinants in that they were able to collaborate with cells expressing only host MHC determinants but not with cells expressing only donor MHC determinants, even though the functional lymphocytes in these chimeras were shown to be of donor origin. Experiments utilizing double donor A + B {arrow} A chimeras further demonstrated that the ability of chimeric T cells to recognize allogeneic MHC determinants as self structures was a function of a radiation-resistant host element and not simply a consequence of the tolerization of T cell precursors to allogeneic MHC determinants, because strain A lymphocytes isolated from A + B {arrow} A chimeras were tolerant to both A and B MHC determinants but were restricted to the self recognition of syngeneic host type A MHC determinants. Finally, the Ir gene phenotype expressed by B10 {arrow} B10.A and B10.A {arrow} B10 chimeric lymphocytes was determined by their ability to function in the Ir gene controlled response to TNP-poly-L-(Tyr,Glu)-poly-D,L-Ala-poly- L-Lys [(T,G)-A--L]. The ability of lymphocytes to function in TNP-(T,G)-A--L responses was not determined by their genotype but rather paralleled the specificity of their self recognition repertoire for high responder (H-2 (b)) determinants. The possible degeneracy of the MHC-specific self recognition repertoire is discussed, and a model is proposed for Ir gene regulation in which expression of Ir gene function by lymphocytes is an antigen-nonspecific consequence of the specificity and cross-reactivity of their self recognition repertoire.

Animals↗
PubMed1981

Cytotoxic T lymphocyte responses by chimeric thymocytes. Self-recognition is determined early in T cell development.

In this study the cytotoxic T lymphocyte (CTL) recognition pattern of thymocytes from recently reconstituted parent leads to F1 and F1 leads to parent radiation bone marrow chimeras was investigated. Chimeric thymocytes were entirely of donor origin approximately 4 wk after irradiation and reconstitution but were not capable of autonomously generating either alloreactive or trinitrophenyl (TNP)-modified-self-reactive CTL responses. However, in the presence of interleukin-2 (I1-2), the the putative T helper cell product, CTL could be generated in vitro by thymocytes from recently reconstituted chimeras. Experiments with thymocytes from A leads to A X B and A X B leads to A chimeras revealed the following: (a) thymocytes from both types of chimeras were nonreactive to either A or B parental major-histocompatibility complex (MHC) determinants even though they were alloreactive to third-party stimulator cells; and (b) thymocytes from these chimeras were restricted to the recognition of TNP in association with MHC determinants syngeneic to the chimeric host. Thus, these experiments demonstrate that even at the earliest time CTL effectors of donor origin from the thymuses of chimeras can be studied, their self-receptor repertoire has already been restricted to recognition of host MHC determinants. These results support the concept that the host environment influences the self-recognition capacity of T cells at the pre- or intrathymic stage of differentiation.

Animals↗
PubMed1981

Functional helper activity of monoclonal T cell populations: antigen-specific and H-2 restricted cloned T cells provide help for in vitro antibody responses to trinitrophenyl-poly(LTyr,Glu)-poly(DLAla)--poly(LLys).

The ability of long-term cultured and monoclonal T cell populations to provide antigen-specific help was assessed in a system of Ir gene-controlled in vitro antibody responses to soluble antigens. T-cell colonies and monoclonal T-cell lines were generated which proliferated specifically in response to poly(LTyr,Glu)-poly(DLAla)--poly(LLys) [(T,G)-A--L] and were I-A restricted in these proliferative responses. These (T,G)-A--L-specific T-cell populations were evaluated for their ability to help unprimed and T-cell depleted spleen cell populations in the generation of antibody responses to trinitrophenyl (TNP)-(T,G)-A--L in vitro. It was found that long-term T-cell lines, including monoclonal T-cell populations derived by limiting dilution, were highly efficient helper cells for IgM responses to TNP-(T,G)-A--L. These helper T cells were both antigen-specific and I-A restricted in their ability to be activated and to cooperate with T-cell depleted spleen cell populations. Once specifically activated, however, these clones provided help that was antigen nonspecific. These studies have thus demonstrated the ability of antigen-specific and H-2-restricted monoclonal T-cell populations to provide help for responses to soluble antigens in vitro.

Animals↗
PubMed1981

The role of H-2 in T cell recognition of Mls.

The role of H-2 was evaluated in T cell recognition of Mls-encoded antigens during primary mixed lymphocyte responses (MLR). Mlsc was used as a stimulating determinant in MLR and its recognition by T cells was assessed by linear regression analysis under culture conditions in which (A x B)F1 responder cell number was the factor limiting total response. Results of such experiments indicated the presence of distinct (A x B)F1 responder T cell subpopulations capable of differentially recognizing the foreign Mls antigen in association with one or the other parental H-2 haplotype. These findings demonstrate that T cells do not recognize Mlsc products in isolation, but rather are restricted to recognition of Mlsc in the context of "self" H-2 determinants.

Animals↗
PubMed1981

T cell recognition in the mixed lymphocyte response. II. Ia-positive splenic adherent cells are required for non-I region-induced stimulation.

Ia-positive splenic adherent cells (SAC) have been shown to be the predominant stimulators of a mixed lymphocyte response (MLR) to whole H-2 differences, in which most of the proliferative response is directed against I region-encoded determinants. The present studies were undertaken to examine the ability of several purified lymphoid subpopulations to activate T cells in response to the non-H-2-linked MIs products or to products of the K or D regions of H-2. The results demonstrated that adherent cell-depleted populations of T and B cells were nonstimulatory, whereas SAC were potent stimulators for responses involving each of these genetic differences. Treatment of these SAC with anti-Ia and C abrogated their MLR-stimulating ability. In contrast, whereas treatment of SAC with anti-Ia and C abrogated their ability to stimulate an MLR directed against K or D region-encoded determinants, this treatment had no effect on their ability to generate a cytotoxic T lymphocyte response against these same determinants. These findings suggest that in addition to presenting allogeneic I region-encoded determinants, Ia-positive SAC also play a unique role in the presentation of non-I region-encoded alloantigens to proliferating T cells.

Animals↗