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

First Author  Eisenbraun MD Year  1999
Journal  J Immunol Volume  163
Issue  5 Pages  2621-7
PubMed ID  10453001 Mgi Jnum  J:57091
Mgi Id  MGI:1343670 Doi  10.4049/jimmunol.163.5.2621
Citation  Eisenbraun MD, et al. (1999) mdr1a-encoded P-glycoprotein is not required for peripheral T cell proliferation, cytokine release, or cytotoxic effector function in mice. J Immunol 163(5):2621-7
abstractText  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-gamma 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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