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MHC Class I Is Required for Peripheral Accumulation of CD8⁺ Thymic Emigrants¹

Dragana Nei and Stanislav Vukmanovi²

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

MHC molecules influence the fate of T lymphocytes at two important stages of their differentiation. Recognition of self peptide/MHC complexes in the thymus determines whether immature T cells should live and mature into immunocompetent T cells or whether they should die. In the periphery, recognition of Ags presented by MHC molecules induces T cell activation, proliferation, and differentiation into effector/memory T cells. We describe in this work a third role that MHC molecules play in T cell physiology. CD8⁺ thymic emigrants require presence of MHC class I molecules in the periphery to seed the peripheral lymphoid organs. Numbers of CD8⁺ T cells are reduced severely in both the thymus and the periphery of ß₂-microglobulin-deficient (ß₂m^-/-) mice. When grafted with wild-type (ß₂m^+/+) thymic epithelium, immature ß₂m^-/- T cells that populate the graft develop into functional mature CD8⁺ cells. However, significant numbers of peripheral CD8⁺ cells in grafted ß₂m^-/- mice can be observed only after injection of MHC class I-expressing cells in the periphery. Thus, naive T cells in the periphery do not passively await antigenic stimulation, but actively engage in interactions with self MHC molecules that may promote their survival.

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