Peripheral Selection of T Cell Repertoires: The Role of Continuous Thymus Output

Abstract

We investigated the role of continuous thymus output in the shaping of mature T cell repertoires by studying in vivo the survival of a single clone of mature Rag2-deficient T cell receptor (TCR) transgenic cells at different stages of activation in the absence or presence of thymus export. In the absence of thymus export, TCR-transgenic lymphocytes survived indefinitely in the peripheral pools. When new lymphocytes were produced in the thymus and migrated to the periphery, resident memory T cells were maintained in constant numbers, whereas naive and self-reactive T cells were replaced by recent thymus migrants. This T cell renewal ensured both the efficiency of recall responses to antigens as memory T cells persisted independently of thymus output, and the capacity of the immune system to respond to new antigen stimulation as the naive T cell pool was continuously renewed. Our results also indicate that thymus export is required to control the number of self-reactive peripheral T cells that may invade the peripheral pools if thymus output fails.