Antigen receptor-mediated anergy in resting T lymphocytes and T cell clones. Correlation with lymphokine secretion patterns.
The goal of these studies was to define the stimuli and factors that control the induction of anergy in unimmunized resting T lymphocytes. Initial experiments, aimed at establishing the system, showed that exposure of Th1 but not Th2 clones to immobilized anti-CD3 leads to a block in autocrine growth factor production and proliferation upon subsequent restimulation with Ag+APC. Anergy is not prevented by accessory cells, suggesting that this model of T cell tolerance may be due to receptor-mediated inhibitory signals, independent of costimulatory molecules. Culture of small (resting) unimmunized T lymphocytes with anti-CD3 +/- IL-2 induces unresponsiveness to restimulation with anti-CD3, but culture with anti-CD3+IL-4, which stimulates the differentiation of resting cells into IL-4 producers, does not induce anergy. Thus, IL-4-producing clones and bulk populations of IL-4-producing T cells are resistant to Ag receptor-mediated inhibitory stimuli. These results provide experimental models for studying the mechanisms of anergy in normal, unselected, mature T cells, and demonstrate fundamental similarities between cloned cell lines and unimmunized T lymphocytes in the induction of anergy.
Williams
M E
ME
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Shea
C M
CM
Lichtman
A H
AH
Abbas
A K
AK
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D017252:CD3 Complex; D002478:Cells, Cultured; D002999:Clone Cells; D004306:Dose-Response Relationship, Immunologic; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000502:physiology; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4