Immunological function of a defined T-cell population tolerized to low-affinity self antigens.
In the thymus there are two major mechanisms of T-lymphocyte tolerance: clonal deletion and clonal inactivation. One important problem underlying the mechanism of clonal inactivation is why unresponsive cells are maintained in the mature peripheral T-cell repertoire. Here we report that transgenic alpha beta T-cells may be tolerized to a self antigen Mls-1a, but still retain proliferative responses for alternative peptide antigens and superantigens. These self-tolerant T cells can also provide immunopathological and memory cytotoxic function in vivo. We propose that high-affinity/avidity self-reactive T cells are deleted in the thymus, whereas lower-affinity/avidity interactions lead to unresponsiveness and define the 'resting threshold' for a given T cell. These low-affinity self-tolerant T cells remain functionally competent for high-affinity foreign antigens, and efficiently eliminate natural pathogens in vivo.
Kawai
K
K
Ontario Cancer Institute, Department of Medical Biophysics and Immunology, Toronto, Canada.
Ohashi
P S
PS
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D002454:Cell Differentiation; D017635:Clonal Anergy; D004768:Enterotoxins / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D016747:Minor Lymphocyte Stimulatory Antigens / Q000276:immunology; D051381:Rats; D017634:Self Tolerance; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D001324:Autoantigens; D004768:Enterotoxins; D006183:H-2 Antigens; D016747:Minor Lymphocyte Stimulatory Antigens; C031818:enterotoxin B, staphylococcal