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,
*
Cellular and Molecular Biology Graduate Program and
Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI 48109; and
Geriatrics Center, Institute of Gerontology, and Department of Veterans Affairs-Geriatric Research, Education, and Clinical Center Medical Center, Ann Arbor, MI 48109
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 that express P-gp goes up with
age, and the P-gp-expressing subset of the CD4 memory population is
hyporesponsive in many in vitro assays. The significance 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 studies revealed that peripheral T cells exclusively utilize the
mdr1a-encoded isoform rather than the homologous
mdr1b or mdr2 isoforms. Comparisons of T
cells from mdr1a+/+ and
mdr1a-/- mice showed no differences in
proliferation or in secretion of IL-2, IL-4, IL-5, IL-10, or IFN-
in
response to polyclonal stimulation. Moreover,
mdr1a-/- T cells produced strong
allospecific cytotoxic responses comparable to those of wt T cells. Our
results show that P-gp is not a necessary component of peripheral T
cell functional responses. Further investigation will be needed to
determine the significance of P-gp expression in T
lymphocytes.
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