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ßTCR⁺ Cells Are a Minimal Fraction of Peripheral CD8⁺ Pool in MHC Class I-Deficient Mice¹

Dragana Nei², Fabio R. Santori and Stanislav Vukmanovi³

Michael Heidelberger Division of Immunology, Department of Pathology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, NY 10016

MHC class I molecules play a role in the maintenance of the naive peripheral CD8⁺ T cell pool. The mechanisms of the peripheral maintenance and the life span of residual CD8⁺ cells present in the periphery of ß₂-microglobulin-deficient (ß₂m^-/-) mice are unknown. We here show that very few CD8⁺ cells in ß₂m^-/- mice coexpress CD8ß, a marker of the thymus-derived CD8⁺ T cells. Most of the CD8⁺ cells express CD11c and can be found in ß₂m/RAG-2 double-deficient mice, demonstrating that these cells do not require rearranged Ag receptors for differentiation and survival and may be of dendritic cell lineage. Rare CD8⁺CD8ß⁺ cells can be detected following in vivo alloantigenic stimulation 2 wk after the adult thymectomy. Selective MHC class I expression by bone marrow-derived cells does not lead to an accumulation of CD8ß⁺ cells in ß₂m^-/- mice. These findings demonstrate that 1) thymic export of CD8⁺ T cells in ß₂m^-/- mice is reduced more severely than previously thought; 2) non-T cells expressing CD8 become prominent when CD8⁺ T cells are virtually absent; 3) at least some ß₂m^-/- CD8⁺ T cells have a life span in the periphery comparable to wild-type CD8⁺ cells; and 4) similar ligands induce positive selection in the thymus and survival of CD8⁺ T cells in the periphery.

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