Altered development of intestinal intraepithelial lymphocytes in P-glycoprotein-deficient mice

Michael D. Eisenbraun, R Lee Mosley, Daniel H. Teitelbaum, Richard A. Miller

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Intraepithelial lymphocytes (IEL) that reside in the intestinal epithelium are known to exhibit phenotypic and functional characteristics that are distinct from other T cells. We have recently shown that peripheral T cells exclusively express an isoform of P-glycoprotein (P-gp) encoded by the mdr1a gene, but do not require mdr1a expression for normal proliferative, cytokine, or cytotoxic responses. In the present study, we have used mdr1-type knockout (KO) mice to demonstrate that IEL also utilize mdr1a, but only preferentially, in that the mdr1b isoform can be expressed in the absence of mdr1a expression. We also report that a high level of P-gp activity appears to be necessary for the normal development of certain IEL subpopulations. In specific, while the total number of IEL was relatively unaffected by the absence of mdr1a expression, the proportions of CD8αβ and TCRαβ+ IEL increased significantly in mdr1a and mdr1a/b KO mice at the expense of CD8αα and TCRγδ+ IEL, respectively. Moreover, these subset alterations also appeared to have functional consequences, in that proliferative, IL-2, and IFN-γ responses of IEL from KO mice were distinct from those of normal IEL. In summary, our data suggest that mdr1a expression is required for the development of certain IEL subpopulations, most notably TCRγδ+ cells, and thereby indirectly influences the balance of T cell subsets in the intestinal epithelium. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)783-795
Number of pages13
JournalDevelopmental and Comparative Immunology
Volume24
Issue number8
DOIs
StatePublished - Dec 1 2000

Fingerprint

P-Glycoprotein
Lymphocytes
Knockout Mice
Lymphocyte Subsets
Intestinal Mucosa
Protein Isoforms
T-Lymphocytes
Lymphocyte Count
T-Lymphocyte Subsets
Interleukin-2
Cytokines
Genes

Keywords

  • Alpha-beta TCR
  • CD8
  • Gamma-delta TCR
  • Knockout mice
  • Mucosa
  • Repertoire development
  • T lymphocytes

ASJC Scopus subject areas

  • Developmental Biology
  • Immunology

Cite this

Altered development of intestinal intraepithelial lymphocytes in P-glycoprotein-deficient mice. / Eisenbraun, Michael D.; Mosley, R Lee; Teitelbaum, Daniel H.; Miller, Richard A.

In: Developmental and Comparative Immunology, Vol. 24, No. 8, 01.12.2000, p. 783-795.

Research output: Contribution to journalArticle

Eisenbraun, Michael D. ; Mosley, R Lee ; Teitelbaum, Daniel H. ; Miller, Richard A. / Altered development of intestinal intraepithelial lymphocytes in P-glycoprotein-deficient mice. In: Developmental and Comparative Immunology. 2000 ; Vol. 24, No. 8. pp. 783-795.
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