Selective bystander proliferation of memory CD4(+) and CD8(+) T cells uponNK T or T cell activation

Ag-experienced or memory T cells have increased reactivity to recall Ag, an d can be distinguished from naive T cells by altered expression of surface markers such as CD44, Memory T cells have a high turnover rate, and CD8(+) memory T cells proliferate upon viral infection, in the presence of IFN-alp ha beta and/or IL-15. In this study, we extend these findings by showing th at activated NKT cells and superantigen-activated T cells induce extensive bystander proliferation of both CD8(+) and CD4(+) memory T cells. Moreover, proliferation of memory T cells can be induced by an IFN-alpha beta-indepe ndent but IFN-gamma- or IL-12-dependent pathway. In these conditions of bys tander activation, proliferating memory (CD44(high)) T cells do not derive from activation of naive (CD44(low)) T cells, but rather from bona fide mem ory CD44(high) T cells. Together, these data demonstrate that distinct path ways can induce bystander proliferation of memory T cells.