Properties of Primed Suppressor T Cells and their Products

The synthetic terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) fails to stimulate development of GAT-specific antibody responses in nonresponder mice but stimulates development of GAT-specific suppressor T cells that inhibit the development of normal anti-GAT plaque-forming cell responses to GAT complexed to methylated bovine serum albumin (MBSA). Extracts from lymphoid cells of GAT-primed but not control, nonresponder (DBA/1) mice contain a T-cell factor (GAT-TsF) that also specifically suppresses responses to GAT-MBSA by normal syngeneic spleen cells. The experiments reported in this communication demonstrate that: (a) extracts from all GAT-primed nonresponder mice tested contain GAT-TsF; (b) non-H-2 genes do not restrict the production of GAT-TsF; (c) all nonresponder strains of mice regardless of their non-H-2 genes are suppressed by GAT-TsF from all other strains bearing the nonresponder H-2p,q,s haplotypes; (d) suppression of GAT-MBSA responses by both syngeneic and allogeneic nonresponder spleen cells is mediated by a molecule encoded by the H-2 gene complex; and (e) both syngeneic and allogeneic nonresponder mice are suppressed by purified GAT-TsF that lacks immunoreactive GAT.

Section: Is Suppression Of Responses By Syngeneic and Allogeneic Splementioning

confidence: 82%

mentioning

confidence: 93%

Immunosuppressive factors from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10. IV. Lack of strain restrictions among allogeneic, nonresponder donors and recipients.

Kapp¹

1978

“…They are not concerned with the general capacity to develop suppression, since DBA/1 (H-211) mice which develop suppressor T cells after GAT immunization are not specifically suppressed by GT and, therefore, lack the GT Is gene . Genetic similarities between H-linked Is and Ir genes are illustrated by the following observations : (a) Ir genes have been shown to be concerned with the expression of helper function in T-cell-dependent responses (6, 7) ; (b) helper and suppressor activity of T cells appear to be two related aspects of the regulatory activity ofthese cells on specific immune responses ; (c) the ability to mount antibody responses in systems under Ir gene control has been shown to be associated with the production of antigen-specific factors produced by responder T cells and endowed with helper activity for B cells (8,9) ; (d) similar antigen-specific factors with specific suppressor activity have been obtained from suppressor T cells (10)(11)(12); and (e) both helper and suppressor factors have similar molecular size and possess antigenic determinants coded for in the I region of the H2 complex (10,11,13).…”

Section: Discussionmentioning

confidence: 99%

Genetic control of specific immune suppression. II. H-2-linked dominant genetic control of immune suppression by the random copolymer L-glutamic acid50-L-tyrosine50 (GT).

Debré¹,

Kapp²,

Dorf³

et al. 1975

102

Several inbred as well as congenic resistant strains of mice, which fail to respond to the random copolymer of L-glutamic acid50-L-tyrosine50 (GT), were shown to develop specific PFC responses when stimulated by GT complexed to an immunogenic carrier such as methylated bovine serum albumin (MBSA). In these studies we have found that GT preimmunization has a tolerogenic effect on the response to GT-MBSA in some mouse strains; whereas in other strains of mice, GT fails to inhibit the GT-MBSA response. We may, therefore, conclude that immune suppression cannot account for nonresponsiveness in all cases. The development of specific immune suppression in response to GT was shown to be inherited as a dominant trait in F1 hybrids resulting from the mating of suppressor with nonsuppressor strains. This trait is, therefore, under the control of a gene or genes that we have designated as specific immune suppression gene(s) Is genes. The strain distribution of GT induced suppression demonstrates that Is genes are coded for in the H-2 complex. Furthermore, immune suppression by the two related copolymers, GT and GAT, are distinct in different strains of mice. The significance of these data for our understanding of the regulation of the immune response is discussed.

“…Lonai has been able to remove this stimulating T cell by treatment with anti-Ia serum and complement (25). Of interest, too, is the finding that the activity of an antigen-specific helper cell replacing factor and an antigen-specific suppressor factor prepared from primed thymocytes can be removed by an Ia immunoabsorbent column (26)(27)(28).…”

Section: Response Of Spleen Cells Resistant Tomentioning

confidence: 99%

Effects of anti-Ia sera on mitogenic responses. II. Differential expression of the Ia marker on phytohemagglutinin and concanavalin A-reactive T cells.

Niederhuber¹,

Frelinger²,

Dine³

et al. 1976

Genes mapping in the I region of the H-2 complex control a system of lymphocyte alloantigens (Ia) which are expressed on a subpopulation of T cells and on most B cells. Specific anti-Ia serum in the presence of rabbit complement removed the splenic T-cell subpopulation responsive to Con-A, but did not affect the response to phytohemagglutinin (PHA) or Leucoagglutinin. Antibodies specific for Ia, H-2K, or H-2D membrane antigens were used without complement to pretreat spleen cells. These antibody pretreated cells responded normally to Con-A and PHA.