Chronic modulation of the TCR repertoire in the lymphoid periphery

Using TCR V beta 5 transgenic mice as a model system, we demonstrate that t he induction of peripheral tolerance can mold the TCR repertoire throughout adult life, In these mice, three distinct populations of peripheral T cell s are affected by chronic selective events in the lymphoid periphery. First , CD4(+)V beta 5(+) T cells are deleted in the lymphoid periphery by supera ntigens encoded by mouse mammary tumor viruses-8 and -9 in an MWC class II- dependent manner. Second, mature CD8(+)V beta 5(+) T cells transit through a CD8(low)V beta 5(low) deletional intermediate during tolerance induction by a process that depends upon neither mouse mammary tumor virus-encoded su perantigens nor MHC class II expression. Third, a population of CD4(-)CD8(- )V beta 5(+) T cells arises in the lymphoid periphery in an age-dependent m anner. We analyzed the TCR V alpha repertoire of each of these cellular com partments in both V beta 5 transgenic and nontransgenic C57BL/6 mice as a f unction of age. This analysis revealed age-related changes in the expressio n of V alpha families among different cellular compartments, highlighting t he dynamic state of the peripheral immune repertoire. Our work indicates th at the chronic processes maintaining peripheral T cell tolerance can dramat ically shape the available TCR repertoire.