Characterization of an endogenous Lyt2+ T-suppressor-cell population regulating autoreactive T cells in vitro and in vivo.
Autoreactive T cells have been defined by their capacity to respond to self-Ia antigens expressed on non-T cells. Several recent studies have suggested that these cells may play important immunoregulatory functions. However, it is not clear what regulates the responsiveness of autoreactive T cells and why such cells are not demonstrably stimulated in vivo, where they are in the constant presence of self-Ia antigens. In the present study we examined the role of T suppressor (Ts) cells in regulating autoreactive T cells. We observed that enhanced autoreactivity occurred in vitro when Lyt2+ T cells were depleted from the responding and/or stimulating spleen cells in a syngeneic mixed-lymphocyte reaction. Similarly, addition of irradiated Lyt2+ T cells but not L3T4+ T cells inhibited the response of L3T4+ T cells to self-Ia antigens. The activity of the suppressor cells was specific to the autoreactive T cells since antigen-specific and alloreactive T-cell proliferation were not inhibited. Furthermore, depletion of Lyt2+ T cells by in vivo treatment of mice with anti-Lyt2 monoclonal antibodies caused enhanced endogenous proliferation of lymph node and splenic T cells and increased the T-cell response to self-Ia antigens in vitro. These studies, therefore, suggest that T-cell tolerance to self-Ia antigens in vivo may be maintained by naturally occurring Lyt2+ Ts. Mice having enhanced autoreactivity may provide a useful tool to address the role of autoreactive T cells in the immune response to foreign antigens and in the pathogenesis of autoimmune diseases.
Nagarkatti
P S
PS
Department of Biology, Virginia Polytechnic Institute, Blacksburg 24061.
Nagarkatti
M
M
Mann
L W
LW
Jones
L A
LA
Kaplan
A M
AM
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007518:Isoantibodies / Q000008:administration & dosage; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D051379:Mice; D008811:Mice, Inbred DBA; D010641:Phenotype; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000145:classification* / Q000276:immunology
D000950:Antigens, Ly; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies; C029805:Lyt antibodies