T cell proliferation, differentiation, and restoration in lymphopenic individuals: for contributed volumes.

Abstract

When a small number of naive T cells are adoptively transferred into syngeneic lymphopenic hosts, such as mice deficient in recombination activating gene-1 (RAG-/-) or sublethally irradiated normal mice, the transferred T cells proliferate, a phenomenon referred to as homeostasis-driven or lymphopenia-induced proliferation. Although deliberate antigen stimulation is not required, homeostatic T cell proliferation requires i) the engagement of T cell receptor (TCR) with self peptide-major histocompatibility complexes (pepMHC) and ii) the presence of lymphopenia (or “space”) (Tanchot et al.,, 1997, Ernst et al., 1999, Viret et al., 1999, Goldrath and Bevan, 1999, Bender et al., 1999). We have shown that following homeostatic proliferation naive CD8 T cells acquire the phenotype and functional properties characteristic of antigen-induced memory T cells. We have also developed an in vitro system for studying homeostatic T cell proliferation. These findings and their implications for memory T cell development and the stable maintenance of naive and memory T cell compartments are discussed.