mdr1a-encoded P-glycoprotein is not required for peripheral T cell proliferation, cytokine release, or cytotoxic effector function in mice

The plasma membrane transport protein P-glycoprotein (P-gp) is expressed by subsets of both CD4+ and CD8+ T cells in mice, The proportion of T cells t hat express P-gp goes up with age, and the P-gp-expressing subset of the CD 4 memory population is hyporesponsive in many in vitro assays. The signific ance of P-gp expression for T cell function has not been well established, although several reports have suggested that it may promote cytokine export and/or cytotoxic T cell function. To elucidate which T cell functions may require P-gp, we have compared a variety of responses using T cells from wt and P-gp knockout mice. Protein expression and rhodamine-123 efflux studie s revealed that peripheral T cells exclusively utilize the mdr1a-encoded is oform rather than the homologous mdr1b or mdr2 isoforms, Comparisons of T c ells from mdr1a(+/+) and mdr1a(-/-)mice showed no differences in proliferat ion or in secretion of IL-2, IL-4, n-5, IL-10, or IFN-gamma in response to polyclonal stimulation. Moreover, mdr1a(-/-) T cells produced strong allosp ecific cytotoxic responses comparable to those of wt T cells. Our results s how that P-gp is not a necessary component of peripheral T cell functional responses. Further investigation will be needed to determine the significan ce of P-gp expression in T lymphocytes.