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Recent studies have suggested that intestinal intraepithelial lymphocytes (iIEL) iIELs are quite different from peripheral T cells in various aspects of their development and functions. By characterizing iIEL subpopulations according to their surface expression of CD4, CD8a, and CD8b chains, we analyzed ab T cell receptor (TCR) Vb chain usage by flow cytometry, and found that, unlike in human iIEL, there is no preferential usage of Vb in murine iIEL. Within the aaCD8 abTCR subpopulation, Vb6+ cells was remained in Mls-1a mice. Similar frequency of Vb14+ CD8+ iIEL was found in Kk mice as in Kb mice. It suggests that selection of abTCR in aaCD8 iIEL during their maturation is different from that of peripheral T cells. Analysis of CD44 and Ly6C expression revealed that not only aaCD8 but abCD8 and CD4 iIEL expressed differently from that of peripheral CD4 and CD8 cells. We further characterize iIEL subpopulations by examining their proliferation activity and cytokine production in response to stimulation via abTCR with or without costimulation of CD28 or CD2. We found that CD4 and abCD8 iIEL proliferate in the presence of exogenous IL2, whereas aaCD8 iIEL showed no proliferative response. The same response pattern was observed for IL2 and IFN-r production after stimulation, even under the condition without exogenous IL2 and no detectable proliferation response. None of the iIEL subpopulations nor lymph node CD8 cells produce IL4 in response to the above stimuli. The present study shows that CD4, abCD8, and aaCD8 iIEL are quite distinct from peripheral T cells in surface marker and functions. Different iIEL subsets may have different function. However, how the unique properties of iIEL relate to their functions in vivo requires further investigation.
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