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Biomedical subjects

R J Hodes

Publications and source records attributed to R J Hodes.

At least 163 records · Page 9Linked to original sources
PubMed1980

Major histocompatibility complex-restricted self recognition. A monoclonal anti-I-Ak reagent blocks helper T cell recognition of self major histocompatibility complex determinants.

The functional role of cell surface Ia antigens has been studied for in vitro antibody responses, using as a probe the ability of anti-Ia reagents to inhibit these responses. A hybridoma monoclonal anti-Ia reagent specific for a product of I-Ak (Ia.17) profoundly inhibited in vitro antibody responses to TNP-KLH by spleen cells of the I-Ak but not I-Ab haplotype. This inhibition by anti-I-Ak product, but not by interaction with T or B cell product, in spite of the fact that functional B cells as well as accessory cells could be shown to express the determinant detected by this hybridoma reagent. These results suggest that the Ia expressed by accessory cells in of unique functional importance in these responses. To further characterize the function of Ia antigens in this response system, the mechanism of anti-I-Ak inhibition was determined. The inhibition resulting from interaction of anti-I-Ak with accessory cell Ia was not mediated by nonspecific suppressor cells, nor was there nonspecific interference with accessory cell function as a result of the binding of anti-Ia antibody. The relationship between anti-Ia inhibition and T helper cell recognition of self determinations on accessory cells was analyzed using T cells from radiation bone marrow chimeras. It was demonstrated that (B10 X B10.A)F1 leads to B10 (F1 leads to B10) chimera T cells were able to cooperate with B10 (H-2b and I-Ab) but not B10.A (H-2a and I-Ak) accessory cells for responses to TNP-KLH; F1 leads to B10.A T cells were able to cooperate with B10.A but not B10 accessory cells; and both chimera populations were able to cooperate with (B10 X B10.A)F1 (F1) accessory cells. Monoclonal anti-I-Ak inhibited the cooperation of F1 leads to B10.A T cells with the same F1 accessory cells. Thus, inhibition by anti-I-Ak is dependent upon active helper T cell recognition of I-Ak-encoded determinants expressed on accessory cells. These findings demonstrate that T cells recognize self Ia determinants expressed on accessory cells, and that such recognition is required for the generation of T cell-dependent antibody responses.

Animals↗
PubMed1980

Cellular and genetic control of antibody responses. VIII. MHC restricted recognition of accessory cells, not B cells, by parent-specific subpopulations of normal F1 T helper cells.

Normal F1 helper T cell populations were analyzed under conditions in which the number of T cells was strictly limiting so that anti-hapten PFC responses to TNP-KLH increased linearly with increasing numbers of T cells. The slope of the response line is a measure of the helper activity of the added T cell population and reflects the number of helper T cells activated. In this way, the recognition and activation requirements of normal F1 helper T cell subpopulations were analyzed. It was determined that the F1 helper T cells specific for recognizing antigen in the context of the MHC determinants of only one parent specifically recognized those determinants expressed on accessory cells, but not on B cells. Indeed, each parent-specific F1 T cell subpopulation was only triggered by one parent's accessory cells; but once triggered, each parent-specific F1 T cell subpopulation was capable of activating either parent's B cells.

Animals↗
PubMed1979

Cellular and genetic control of antibody responses. V. Helper T-cell recognition of H-2 determinants on accessory cells but not B cells.

Requirements for helper T-cell recognition of H-2 determinants expressed on adherent accessory cells and on B cells was individually assessed in the anti-hapten PFC responses to TNP-KLH. Complicating allogeneic effects were minimized or avoided by the use of helper T cells from normal F1 hybrids, parent leads to F1 chimeras, and F1 leads to parent chimeras. The results of both in vitro and in vivo experiments demonstrated that: (a) helper T cells are not required to recognize the identical H-2 determinants on both accessory cells and B cells; (b) helper T cells are required to recognize K or I-A region-encoded determinants expressed on accessory cells; (c) no requirement was observed in vitro or in vivo for helper T-cell recognition of B-cell-expressed H-2 determinants; and (d) no requirement was observed for H-2 homology between accessory cells and B cells. The absence of required helper T-cell recognition of the identical H-2 determinants on both accessory cells and B cells was demonstrated in two ways: (a) naive of KLH-primed (A x B)F1 hybrid helper T cells collaborated equally well with B cells from either parentA or parentB in the presence of accessory cells from either parent; (b) A leads to (A x B)F1 chimeric spleen cells depleted of accessory cells collaborated equally well with accessory cells from either parentA or parentB, even though the B cells only expressed the H-2 determinants of parentA. A requirement for helper T-cell recognition of K or I-A region-encoded H-2 determinants on accessory cells was also demonstrated in two ways: (a) (A x B)F1 leads to parentA chimeric spleen cells depleted of accessory cells collaborated with accessory cells from parentA but not parentB; and (b) (A x B)F1 leads to parentA chimeric helper T cells collaborated with normal F1 B cells only in the presence of parental or recombinant accessory cells that expressed the K or I-A region-encoded determinants of parentA. Although restricted in their ability to recognize H-2 determinants on accessory cells, it was demonstrated both in vitro and in vivo that (A x B)F1 leads to parentA chimeric helper T cells were able to collaborate with B cells from either parentA or parentB. In vitro in the presence of accessory cells from parentA, (A x B)F1 leads to parentA chimeric helper T cells collaborated equally well with B cells from either parent. In addition, the inability of (A x B)F1 leads to parentA chimeric helper T cells to collaborate with (B + accessory) cells from parentB was successfully reversed by the addition of parentA SAC as added accessory cells. In vivo, upon the addition of parentA accessory cells, (A x B)F1 leads to parentA chimeric helper T cells collaborated with parentB B cells in short-term adoptive transfer experiments.

Animals↗
PubMed1979

T cell recognition in the mixed lymphocyte response. I. Non-T, radiation-resistant splenic adherent cells are the predominant stimulators in the murine mixed lymphocyte reaction.

The ability of subpopulations of murine spleen cells to stimulate a mixed lymphocyte response (MLR) was studied. It was found that T cells (nylon-nonadherent spleen cells) and B cells [G-10 passed and treated with rabbit anti-mouse brain serum (RAMB) and complement (C)] were poor stimulators of an MLR. In contrast, whole spleen cells or B cells plus adherent cells (RAMB +C-treated spleen cells) produced good stimulation. However, a non-T, radiation-resistant splenic adherent cell (SAC) population was up to 20 to 50 times more efficient as a stimulator of an MLR on a per cell basis than an unseparated spleen population. These SAC were shown to express Ia determinants encoded by genes in I-A and I-E/C. These results suggest that Ia+ SAC may be the predominant stimulating cells in spleen cell populations, and the preferential target for T cell recognition in cell interaction events.

Animals↗
PubMed1978

Cellular and genetic control of antibody responses in vitro. III. Immune response gene regulation of accessory cell function.

The possibility was investigated that Ir genes regulate the function of cells other than T or B cells in the primary IgM responses to the synthetic antigens trinitrophenylated poly-L-(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys [TNP-(T,G)-A--L]and trinitrophenylated poly-,-(His,Glu)-poly-D, L-Ala--poly-L-Lys [TNP-(H,G)-A--L]. The primary responses of (B10 x B10.A)F(1) spleen cells to both antigens were abrogated by Sephadex G-10 passage, and restored by the addition of spleen adherent cells. The cell type in the spleen adherent cell population active in reconstituting the responses to TNP-(T,G)-A--L and TNP-(H,G)-A--L was a non-T, non-B, radiation-resistant, glass-adherent spleen cell. The responses of Sephadex G-10-passed (responder x nonresponder)F(1) spleen cells to TNP-(T,G)-A--L or TNP-(H,G)-A--L were reconstituted by spleen adherent cells from only responder strains. Spleen adherent cells from F(1) mice reconstituted the responses to both antigens. Spleen adherent cells from each of the strains tested reconstituted the non- Ir gene-controlled response to a third antigen, TNP-keyhole limpet hemocyanin. The inability of spleen adherent cells from nonresponder strains to reconstitute the responses to either TNP-(T,G)-A--L or TNP-(H,G)-A--L was not a result of active suppression induced by the presence of nonresponder adherent cells, since a mixture of responder and nonresponder spleen adherent cells reconstituted the responses to both antigens. The use of spleen adherent cells from recombinant strains demonstrated that the autosomal dominant genes controlling the ability of spleen adherent cells to function as accessory cells in the responses to TNP-(T,G)-A--L and TNP-(H,G)-A--L are located in the K or I-A regions of the responder H-2 complex, the same region(s) of H-2 as the Ir genes controlling overall in vitro and in vivo responsiveness to these antigens.

Animals↗
PubMed1978

Genetic analysis of Ia determinants expressed on Con A-reactive cells.

Pretreatment of mouse lymphoid cells with anti-Ia sera and C abrogated the proliferative responses of these cells to Con A. Studies were carried out with several anti-Ia reagents and intra-H-2 recombinant mouse strains to map the I subregion(s) whose products are expressed on Con A-reactive cells. Treatment with a (B10.A X A)F1 anti-B10 reagent and C abrogated the ability of BALB/c cells to respond to Con A. Absorption studies on this reagent demonstrated that Con A-reactive cells express Ia determinants coded by the I-A subregion. The results with two additional reagents, B10.A(4R) anti-B10.A(2R) tested on B10.BR cells and (B10 X D2.GD)F1 anti-B10.D2 absorbed with B10.A cells and tested on BALB/c cells, demonstrated that Con A-reactive cells also express Ia determinants encoded to the right of I-A. Several antisera and strain combinations were evaluated in which the antisera could contain antibodies specific for products of genes encoded by the I-J subregion, but the results were inconclusive. These data demonstrate that there are at least two different I subregions, one in I-A and one to the right of I-A, that code for antigens expressed on Con A-reactive cells.

Animals↗
PubMed1978

Requirement for an Ia-bearing accessory cell in Con A-induced T cell proliferation.

Pretreatment of murine lymphoid cells with anti-Ia and C abrogated the proliferative response of these cells to Con A, but not to PHA. Reconstitution experiments demonstrated that T cell-enriched populations failed to restore Con A responsiveness and that T cell-depleted populations were more effective in restoring responsiveness to Con A. In particular, a population of 1000 R resistant, glass-adherent, non-T spleen cells was capable of completely restoring responsiveness to Con A when added in numbers as low as 4% of cultured cells. These splenic adherent cells were found to express Ia determinants encoded by at least two genes: one in I-A and the other in I-B, I-J, and/or I-E/C, and it was demonstrated that determinants encoded in these two regions were expressed on the same cell. These results demonstrate that non-T accessory cells may be the Ia+ cells entirely responsible for the anti-Ia and C-induced abrogation of T cell proliferative responses to Con A.

Animals↗
PubMed1977

Cellular and genetic control of antibody responses in vitro. II. Ir gene control of primary IgM responses to trinitrophenyl conjugates of poly-L-(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys and poly-L-(His,Glu)-poly-D,L-Ala--poly-L-Lys.

The in vitro primary IgM anti-hapten responses to trinitrophenyl (TNP) conjugates of poly-L-(Tyr,Glu)-poly-D,L-Ala-poly-L-Lys (T,G)-A--L and poly-L(His,Glu)-poly-D,L-Ala--poly-L-Lys (H,G)-A--L were shown to be T-cell dependent and under autosomal dominant H-2-linked Ir gene control which mapped within the K or I-A regions of the H-2 complex. The in vitro response to TNP-keyhole limpet hemocyanin, while T-dependent, was not under demonstrable genetic control. The genes governing the in vitro primary IgM anti-hapten responses to TNP-(T,G)-A--L and TNP-(H,G)-A--L resemble the Ir genes controlling the in vivo secondary IgG responses to (T,G)-A--L and (H,G)-A--L in that they are autosomal dominant, map identically within the H-2 complex, and have identical responder and nonresponder haplotypes. It is concluded that Ir genes can govern the ability to generate an IgM response upon initial exposure to antigen.

Alanine↗
PubMed1977

Effect of tumor cells on the generation of cytotoxic T lymphocytes in vitro. I. Accessory cell functions of mouse tumor cells in the generation of cytotoxic T lymphocytes in vitro: replacement of adherent phagocytic cells by tumor cells or 2-mercaptoethanol.

In agreement with previous reports, the primary in vitro response to alloantigens has been shown to be dependent on the presence of macrophages (Mphs). Splenocytes extensively depleted of adherent phagocytic cells did not generate cytotoxic T lymphocytes, and this activity could be completely restored by small numbers of adherent peritoneal cells (accessory cells). Either P388D1 (Mph-like tumor), P388 ("null" tumor) or P815 (mastocytoma) tumor cells, or 2-mercaptoethanol, could completely replace the accessory function normally mediated by accessory cells. These tumor cells did not non-specifically "enhance" the cytotoxic activity generated with normal nondepleted spleen cells. The restored cultures maintained killing specificity to H-2 targets which was mediated by effector T cells as shown by sensitivity to anti-theta and complement. Therefore, Mphs seem not to be the sole cells capable of mediating an accessory function in a primary response to alloantigens in vitro.

Animals↗
PubMed1977

Regulatory mechanisms in cell-mediated immune responses. II. Comparison of culture-induced and alloantigen-induced suppressor cells in MLR and CML.

Two antigen-nonspecific T cell-dependent suppressor systems were compared for their effects upon CML and MLR. Suppressor cells generated by an in vitro culture of spleen cells were compared with suppressor cells generated by in vivo priming with alloantigen. Culture-induced suppressor cells were themselves unable to respond in CML or MLR; were able to suppress actively the CML and MLR responses of untreated responding cells; were mitomycin-sensitive; and, produced no easily demonstrable suppressive supernatant. Alloantigen-primed cells were able to respond in CML and LR; could suppress proliferation in MLR, but were able to suppress CML only after mitomycin treatment; and, produced suppressive supernatants active in suppressing both CML and MLR. In addition to cataloging the differences and similarities between these suppressor populations, the data have been employed to analyze the mechanisms by which suppression occurs in CML and MLR.

Animals↗
PubMed1976

Mixed lymphocyte reactivity and cell-mediated lympholysis to D-end differences of the murine major histocompatibility complex. Comparison of in vitro responses to exclusive D-end or more extensive MHC differences.

In vitro mixed lymphocyte culture (MLC) responses and the in vitro induction of cell-mediated lympholysis (CML) were studied in congenic strain combinations in which the responding and stimulating strains differed either at the entire major histocompatibility complex (MHC) or only at the D end of the MHC. In contrast to previously reported studies, the relative strengths of stimulation by 'D end only' differences or by whole MHC differences were examined by stimulating identical responding populations with titrated numbers of stimulating cells that differed from the responder either at the D end only or over the entire MHC. When tested in this manner isolated D-end differences were sufficient to generate significant MLC and CML responses in each combination tested. Several 'D end only' differences (the responses of B10.A to B10.A(2R); of B10.A(2R) to B10.A; of B10.D2 to B10.HTG; and of B10.HTG to B10.D2 were several fold less efficient in stimulating MLC and CML responses than were control stimulating cells differing over the whole MHC. In contrast, when the mutant D-end allele da was present on the stimulating cell (the responses of B10.D2 to B10.D2(M504) and of B10 to B10.D2(R106)), stimulation by an isolated D-end difference was comparable to stimulation by broader MHC differences. These findings are discussed in terms of the possible functional complexity of the D region.

Animals↗