High cell density provides potent survival signals for resting T-cells

Activated T-cells are susceptible to apoptosis through two particularly imp ortant pathways: ligation of CD95 (Fas/Apo-1) or cytokine deprivation. Rest ing T-cells have until recently been considered to be relatively resistant to apoptosis. In this report we show that resting T-cells die rapidly by ap optosis when deprived of serum or cell contact. Primed CD45RO+ cells were m ore susceptible than naive CD45RA+ cells, consistent with their relative ex pression of Bcl-2. CD4+, CD8+ and gamma delta T-cells were equally prone to apoptosis under all studied conditions. A linear relationship between cell survival and serum concentration was observed for cells cultured between 0 .5-2 x 10(6)/ml. T-cells cultured at low density died even in high concentr ations of serum. However, resting T-cells cultured at high cell density (4 x 10(6)/ml) survived for extended periods in the absence of serum or other survival factors. This effect was mediated by the production of soluble fac tors and independent of integrin mediated signals. These results suggest th at T-cells at sites of high density such as the lymph node paracortex are i ndependent of external survival factors, while those trafficking through th e peripheral circulation are highly dependent on serum derived factors for survival.