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The Journal of Immunology, 2004, 172: 2238-2246.
Copyright © 2004 by The American Association of Immunologists

Antigen Nonspecific Suppression of T Cell Responses by Activated Stimulation-Refractory CD4+ T Cells 1

Christine T. Duthoit*, Phuong Nguyen* and Terrence L. Geiger2,*,{dagger}

* Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105; and {dagger} Department of Pathology, University of Tennessee School of Medicine, Memphis, TN 38163

Several classes of anergic T cells are capable of suppressing naive T cell proliferation and thereby limiting immune responses. Activated T cells, although not anergic, are transiently refractory to restimulation with Ag. We examine in this study whether activated refractory murine T cells can also suppress naive T cell responses. We find that they can, and that they exhibit many of the suppressive properties of anergic T cells. The activated cells strongly diminish Ag-mediated T cell proliferation, an activity that correlates with their refractory period. Suppression is independent of APC numbers and requires cell contact or proximity. Naive T cells stimulated in the presence of activated refractory cells up-regulate CD25 and CD69, but fail to produce IL-2. The addition of IL-2 to culture medium, however, does not prevent the suppression, which is therefore not solely due to the absence of this growth factor. Persistence of the suppressor cells is also not essential. T cells stimulated in their presence and then isolated from them and cultured do not divide. The suppressive cells, however, do not confer a refractory or anergic state on the target T lymphocytes, which can fully respond to antigenic stimulation if removed from the suppressors. Our results therefore provide evidence that activated T cells act as transient suppressor cells, severely constraining bystander T cell stimulation and thereby restricting their response. These results have potentially broad implications for the development and regulation of immune responses.




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