Journal of Experimental Medicine, Vol 168, 2165-2181, Copyright © 1988 by Rockefeller University Press

ARTICLES

Functional heterogeneity of L3T4+ T cells in MRL-lpr/lpr mice. L3T4+ T cells suppress major histocompatibility complex-self-restricted L3T4+ T helper cell function in association with autoimmunity

CS Via and GM Shearer
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.

The present study demonstrates in MRl-lpr/lpr autoimmune mice an age- dependent loss of MHC-self-restricted function by L3T4+ Th. This defect is not present in age-matched, congenic MRL-+/+ spleen cells and appears to be due to the presence of suppressor cells that are selective for L3T4+ Th and not for Lyt-2+ Th. Surprisingly, the suppressor cells are also L3T4+ T cells and can suppress the IL-2 production of congenic MRL/+ L3T4+ Th to MHC-self-restricted antigens. These data support the idea of functional specialization within the L3T4+ population of T cells. Because L3T4+ suppressor cells are detected late in the course of autoimmunity, we interpret their presence not as a primary initiating event in the development of autoimmunity, but rather as a compensatory mechanism. Additionally, similar suppression of L3T4+ Th function has also been reported in a murine graft-vs.-host model of autoimmunity, suggesting that the suppressor cells represent an immunoregulatory mechanism that is a common feature of autoimmunity. Since excessive class II-restricted Th activity for B cells has been reported for both models of autoimmunity, L3T4+ suppressor cells may represent an attempt to down regulate such excessive Th activity. These findings may be relevant to human autoimmune diseases, such as systemic lupus erythematosus, in which B cell hyperactivity is also associated with reduced IL-2 production by Th.
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This article has been cited by other articles:

• Puliaeva, I., Puliaev, R., Shustov, A., Haas, M., Via, C. S. (2008). Fas Expression on Antigen-Specific T Cells Has Costimulatory, Helper, and Down-Regulatory Functions In Vivo for Cytotoxic T Cell Responses but Not for T Cell-Dependent B Cell Responses. J. Immunol. 181: 5912-5929 [Abstract] [Full Text]  
• Shustov, A., Nguyen, P., Finkelman, F., Elkon, K. B., Via, C. S. (1998). Differential Expression of Fas and Fas Ligand in Acute and Chronic Graft-Versus-Host Disease: Up-Regulation of Fas and Fas Ligand Requires CD8+ T Cell Activation and IFN-{gamma} Production. J. Immunol. 161: 2848-2855 [Abstract] [Full Text]  

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