Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. IV. Special subregion assignment of the gene(s) that codes for the suppressive T-cell factor in the H-2 histocompatibility complex.

The synthetic terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) fails to stimulate development of GAT-specific antibody responses in nonresponder strains of mice, but does stimulate the development of GAT-specific suppressor T cells that inhibit the development of normal anti-GAT antibody responses to GAT complexed to methylated bovine serum albumin (GAT-MBSA). Furthermore, extracts prepared from lymphoid cells of GAT-primed, but not control, nonresponder mice inhibit the development of antibody responses to GAT-MBSA by normal nonresponder mice. This suppression is specific, dose-dependent, and can be readily analyzed in vitro. The suppressive factor is a T-cell product. An extract from GAT-primed DBA/1 mice inhibits the response to GAT-MBSA by spleen cells from histoincompatible strains of mice that are nonresponders to GAT, but not strains that are responders to GAT.

Section: Discussionmentioning

confidence: 99%

Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) II. Cellular source and effect on responder and nonresponder mice.

Kapp¹,

Pierce²,

Benacerraf³

1977

“…These two Ts cell systems, although independent phenomena, shared some characteristics; both are examples of Ts cells not restricted by the I-J subregion of the H-2 complex, in contrast to antigen specific Ts cells (24,25). These Ts cells, however, are stimulated and interact with target cells in a genetically restricted manner controlled by the I-A subregions.…”

Section: Genetic Restrictions On Haplotype-specific Ts Cell Activitymentioning

confidence: 99%

Haplotype-specific suppression of antibody responses in vitro. I. Generation of genetically restricted suppressor T cells by neonatal treatment with semiallogeneic spleen cells

Sorensen¹,

Pierce²

1981

C57BL/10 mice were injected with semiallogeneic (B10.D2 X C57BL/10)F(1) spleen cells via the anterior facial vein within 24 h of birth to induce tolerance to B10.D2 (H-2(d)) alloantigens. Spleen cells from these mice as adults developed reduced, but significant, mixed lymphocyte and cytotoxic lymphocyte responses in vitro to H-2(d) stimulator cells and these treated mice rejected first-set B10.D2 skin grafts within a normal time-course, indicating that at best only a state of partial tolerance had been induced. Spleen cells from these mice failed to develop antibody responses to a variety of antigens in vitro when H-2(d) macrophages were in the cultures. Partially purified T cells from these neonatally treated mice suppressed primary antibody responses by normal syngeneic spleen cells in the presence of H-2(d) but not other allogeneic macrophages. These radiosensitive, haplotype-specific suppressor T (Ts) cells inhibited primary antibody responses by blocking initiation of the response, but failed to suppress secondary antibody responses and mixed lymphocyte or cytotoxic lymphocyte responses by appropriate responding spleen cells. To activate H-2(d) haplotype-specific Ts cells, stimulation with IA(d) subregion antigen(s) was necessary and sufficient; syngenicity at the I-A subregion of H-2 between the activated Ts cells and target responding spleen cell populations was also necessary and sufficient to achieve suppression. Comparable results have been obtained with spleen cells from BALB/c mice injected as neonates with (B10.D2 × C57BL/10)F(1) spleen cells where IA(b) antigens activate the haplotype-specific Ts cells. Implications for the significance of this population of haplotype-specific Ts cells in immune regulation are discussed and the properties of these Ts cells are compared and contrasted with other antigen-specific and nonspecific Ts cells whose activity is restricted by I- region products.

“…Thirdly, our previous studies (3,8,22,24) have demonstrated that various alloantibodies directed against I-J products have the capacity to absorb the KLH-specific suppressor factors from primed splenic T cells and KLH=specific suppressor hybridomas. Similar observations have been reported by several other investigators with different systems (reviewed in 2).…”

Section: Discussionmentioning

confidence: 99%

Monoclonal antibodies that recognize the product controlled by a gene in the I-J subregion of the mouse H-2 complex.

Kanno¹,

Kobayashi²,

Tokuhisa³

et al. 1981

Self Cite

The product of gene(s) in the I-J subregion of the mouse H-2 complex that are expressed on allotype-specific and antigen-specific suppressor T cells has been defined (1; reviewed in 2). The soluble factors derived from antigen-specific suppressor T cells have also been found to bear the I-J subregion gene product (3-8). However, it has not been determined whether the I-J product on the antigen-specific suppressor T cells is the same as that on the antigen-specific suppressor T cell factor. Moreover, recent studies have shown that conventional anti-I-J alloantisera detect the cell surface markers on some helper T cells (9), concanavalin A (Con A)X-induced T cells (10) and some antigen-presenting cells (11). Tada et al. (9), especially, have demonstrated that the absorption of anti-I-J antisera with Lyt-l-positive splenic T cells resulted in the loss of ability to remove the helper (Th2) T cell function, whereas the absorbed anti-I-J still preserved the capacity to eliminate the suppressor activity. Thus, they proposed that the I-J product expressed on the antigen-specific suppressor T cells is distinct from that on the helper T cells. Therefore, it seems most likely that two or more genes rather than a single gene are accommodated in the l-J subregion.