Homeostasis of T cell diversity

Abstract

T cell homeostasis commonly refers to the maintenance of relatively stable T cell numbers in the peripheral lymphoid organs. Among the large numbers of T cells in the periphery, T cells exhibit structural diversity, i.e., the expression of a diverse repertoire of T cell receptors (TCRs), and functional diversity, i.e., the presence of T cells at naive, effector, and memory developmental stages. Although the homeostasis of T cell numbers has been extensively studied, investigation of the mechanisms underlying the maintenance of structural and functional diversity of T cells is still at an early stage. The fundamental feature throughout T cell development is the interaction between the TCR and either self or foreign peptides in association with MHC molecules. In this review, we present evidence showing that homeostasis of T cell number and diversity is mediated through competition for limiting resources. The number of T cells is maintained through competition for limiting cytokines, whereas the diversity of T cells is maintained by competition for self-peptide-MHC complexes. In other words, diversity of the self-peptide repertoire limits the structural (TCR) diversity of a T cell population. We speculate that cognate low affinity self-peptides, acting as weak agonists and antagonists, regulate the homeostasis of T cell diversity whereas non-cognate or null peptides which are extremely abundant for any given TCR, may contribute to the homeostasis of T cell number by providing survival signals. Moreover, self-peptides and cytokines may form specialized niches for the regulation of T cell homeostasis.