Anergic CD8⁺ T Cells Can Persist and Function In Vivo

Abstract

Using a mouse model system, we demonstrate that anergic CD8⁺ T cells can persist and retain some functional capabilities in vivo, even after the induction of tolerance. In TCR Vβ5 transgenic mice, mature CD8⁺Vβ5⁺ T cells transit through a CD8^lowVβ5^low deletional intermediate during tolerance induction. CD8^low cells are characterized by an activated phenotype, are functionally compromised in vitro, and are slated for deletion in vivo. We now demonstrate that CD8^low cells derive from a proliferative compartment, but do not divide in vivo. CD8^low cells persist in vivo 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 capable of producing IFN-γ in vivo despite their inability to proliferate or to kill target cells in vitro. CD8^low cells also accumulate at sites of inflammation, where they produce IFN-γ. Therefore, rather than withdrawing from the pool of functional CD8⁺ T cells, anergic CD8^low cells retain a potential regulatory role despite losing their capacity to proliferate. The ability of anergic cells to persist and function in vivo adds another level of complexity to the process of tolerance induction in the lymphoid periphery.