Immunoregulatory T cell circuits in man. Identification of a distinct T cell subpopulation of the helper/inducer lineage that amplifies the development of alloantigen-specific suppressor T cells.
Regulation of the immune response in man is dependent on interactions between cells of helper/inducer (Leu-3+/T4+) lineage and cells of suppressor/cytotoxic (Leu-2+/T8+) lineage. By using the mixed leukocyte reaction (MLR) as a model system, we have shown previously that alloantigen-primed Leu-3+ cells induce autologous Leu-2+ cells to differentiate into suppressor T cells that specifically inhibit the response of fresh T cells to the original allogeneic stimulator cells. The current study was undertaken to analyze the roles in this suppressor circuit of subpopulations of Leu-3+ cells distinguished from one another on the basis of their binding or lack of binding to monoclonal anti-Leu-8 antibody. Although both Leu-3+,8- and Leu-3+,8+ T cells proliferated in allogeneic MLR, alloactivated Leu-3+,8+ cells alone induced proliferation and differentiation of Leu-2+ suppressor cells. Leu-3+,8+ cells also induced Leu-3+,8- cells to proliferate, and following their activation in this manner, such autoactivated Leu-3+,8- cells augmented the differentiation of Leu-2+ suppressor cells, but only in the presence of alloactivated Leu-3+,8+ cells. Furthermore, this effect, like the suppressor effect, was specific for the inducer cells, and thus indirectly for the HLA-DR antigens of the original allogeneic stimulator cells as well. These results indicate that alloantigen-primed Leu-3+,8+ cells not only activate specific Leu-2+ suppressor cells but also activate specific Leu-3+,8- suppressor-amplifier cells, and in combination, these cells exert potent feedback inhibition of MLR.
Damle
N K
NK
Mohagheghpour
N
N
Kansas
G S
GS
Fishwild
D M
DM
Engleman
E G
EG
D000911:Antibodies, Monoclonal; D002469:Cell Separation; D002478:Cells, Cultured; D004261:DNA Replication; D006801:Humans; D007111:Immunity, Cellular; D007519:Isoantigens / Q000276:immunology*; D007700:Kinetics; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000166:cytology; D012397:Rosette Formation; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007519:Isoantigens