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

被引:30
作者
Eisenbraun, MD
Mosley, RL
Teitelbaum, DH
Miller, RA
机构
[1] Univ Michigan, Sch Med, Cellular & Mol Biol Grad Program, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA
[3] Univ Michigan, CS Mott Childrens Hosp, Dept Surg, Pediat Surg Sect, Ann Arbor, MI 48109 USA
[4] Vet Affairs Med Ctr, Geriatr Ctr, Inst Gerontol, Ann Arbor, MI 48109 USA
关键词
alpha-beta TCR; CD8; gamma-delta TCR; knockout mice; mucosa; repertoire development; T lymphocytes;
D O I
10.1016/S0145-305X(00)00029-X
中图分类号
S9 [水产、渔业];
学科分类号
0908 ;
摘要
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 CD8 alpha beta and TCR alpha beta+ IEL increased significantly in mdr1a and mdr1a/b KO mice at the expense of CD8 alpha alpha and TCR gamma delta+ IEL, respectively. Moreover. these subset alterations also appeared to have functional consequences, in that proliferative, IL-2. and IFN-gamma 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 TCR gamma delta+ cells, and thereby indirectly influences the balance of T cell subsets in the intestinal epithelium. (C) 2000 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:783 / 795
页数:13
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