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Chronic Modulation of the TCR Repertoire in the Lymphoid Periphery¹

Department of Immunology, School of Medicine, University of Washington, Seattle, WA 98195

Using TCR Vß5 transgenic mice as a model system, we demonstrate that the induction of peripheral tolerance can mold the TCR repertoire throughout adult life. In these mice, three distinct populations of peripheral T cells are affected by chronic selective events in the lymphoid periphery. First, CD4⁺Vß5⁺ T cells are deleted in the lymphoid periphery by superantigens encoded by mouse mammary tumor viruses-8 and -9 in an MHC class II-dependent manner. Second, mature CD8⁺Vß5⁺ T cells transit through a CD8^lowVß5^low deletional intermediate during tolerance induction by a process that depends upon neither mouse mammary tumor virus-encoded superantigens nor MHC class II expression. Third, a population of CD4^-CD8^-Vß5⁺ T cells arises in the lymphoid periphery in an age-dependent manner. We analyzed the TCR V repertoire of each of these cellular compartments in both Vß5 transgenic and nontransgenic C57BL/6 mice as a function of age. This analysis revealed age-related changes in the expression of V families among different cellular compartments, highlighting the dynamic state of the peripheral immune repertoire. Our work indicates that the chronic processes maintaining peripheral T cell tolerance can dramatically shape the available TCR repertoire.

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