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The Journal of Immunology, 2002, 168: 6022-6031.
Copyright © 2002 by The American Association of Immunologists

Dynamic Regulation of T Cell Immunity by CD431

Thandi M. Onami*, Laurie E. Harrington*, Matthew A. Williams{dagger}, Marisa Galvan§, Christian P. Larsen{dagger}, Thomas C. Pearson{dagger}, N. Manjunath, Linda G. Baum§, Brad D. Pearce{ddagger} and Rafi Ahmed2,*

* Emory Vaccine Center and Department of Microbiology and Immunology, {dagger} Department of Surgery, Carlos and Marguerite Mason Transplantation Research Center, and {ddagger} Department of Psychiatry, Emory School of Medicine, Atlanta, GA 30322; § Department of Pathology and Laboratory Medicine, University of California School of Medicine, Los Angeles, CA 90095; and Center for Blood Research, Harvard School of Medicine, Boston, MA 02115

During a viral response, Ag-specific effector T cells show dramatically increased binding by the mAb 1B11 and the lectin peanut agglutinin (PNA). We investigated the contribution of CD43 expression to 1B11 and PNA binding as well as its role in generation and maintenance of a CD8 T cell response. Analysis of CD43-/- mice revealed no increased 1B11 binding and reduced PNA binding on virus-specific CD8 T cells from -/- mice compared with +/+ mice. Furthermore, we examined the role of CD43 in the kinetics of an immune response. We show that CD43 expression modestly effects generation of a primary virus-specific CD8 T cell response in vivo but plays a more significant role in trafficking of CD8 T cells to tissues such as the brain. More interestingly, CD43 plays a role in the contraction of the immune response, with CD43-/- mice showing increased numbers of Ag-specific CD8 T cells following initial expansion. Following the peak of expansion, Ag-specific CD8 T cells from -/- mice show similar proliferation but demonstrate increased Bcl-2 levels and decreased apoptosis of Ag-specific effector CD8 T cells in vitro. Consistent with a delay in the down-modulation of the immune response, following chronic viral infection CD43-/- mice show increased morbidity. These data suggest a dynamic role of CD43 during an immune response: a positive regulatory role in costimulation and trafficking of T cells to the CNS and a negative regulatory role in the down-modulation of an immune response.







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