Autologous regulation of naive T cell homeostasis within the T cell compartment

Naive T cells undergo spontaneous slow proliferation on adoptive transfer i nto syngeneic T cell (T)-deficient hosts, Recent work has shown that such " homeostatic" T cell proliferation is driven by MHC molecules loaded with se lf-peptides rather than foreign peptides, Because naive T cells in normal T -sufficient hosts remain in interphase despite continuous contact with self -MHC/peptide ligands, T cells apparently inhibit homeostatic proliferation of neighboring T cells, To address this, we have investigated the requireme nts necessary for "bystander" T cells to inhibit homeostatic proliferation of other T cells. Three key findings are reported. First, homeostatic proli feration of T cells only occurs in specific microenvironments, namely the T cell compartment of the secondary lymphoid tissues. Second, direct entry i nto T cell compartments is also required for bystander inhibition of homeos tatic proliferation. Third, bystander inhibition is mediated largely by nai ve rather than activated/memory T cells and does not require proliferation or TCR ligation. These findings suggest that homeostasis of naive T cells i s unlikely to be regulated through competition for systemic soluble factors or for specific stimulatory self-MHC/peptide ligands, Rather, the data fav or mechanisms that involve competition for local non-MHC stimulatory factor s or direct cell-to cell interactions between the T cells themselves within the T cell compartment. The Journal of Immunology, 2001, 166: 2460-2468.