Anergic CD8(+) T cells can persist and function in vivo

Using a mouse model system, we demonstrate that anergic CD8(+) T cells can persist and retain some functional capabilities in vivo, even after the ind uction of tolerance, In TCR V beta 5 transgenic mice, mature CD8(+)V beta 5 (+) T cells transit through a CD8(low)V beta 5(low) deletional intermediate during tolerance induction. CD8(low) cells are characterized by an activat ed phenotype, are functionally compromised in vitro, and are slated for del etion in vivo. We now demonstrate that CD8(low) cells derive from a prolife rative compartment, but do not divide in vivo. CD8(low) cells persist in vi vo with a t(1/2) of 3-5 days, in contrast to their in vitro t(1/2) of 0.5-1 day. During this unexpectedly long in vivo life span, CD8(low) cells are c apable of producing IFN-gamma in vivo despite their inability to proliferat e or to kill target cells in vitro. CD8(low) cells also accumulate at sites of inflammation, where they produce IFN-gamma. Therefore, rather than with drawing from the pool of functional CD8(+) T cells, anergic CD8(low) cells retain a potential regulatory role despite losing their capacity to prolife rate. The ability of anergic cells to persist and function in vivo adds ano ther level of complexity to the process of tolerance induction in the lymph oid periphery.