INTRAEPITHELIAL LYMPHOCYTES IN HUMAN CUT HAVE LYTIC POTENTIAL AND A CYTOKINE PROFILE THAT SUGGEST T-HELPER 1 AND CYTOTOXIC FUNCTIONS

The functional properties of intraepithelial lymphocytes (IEL) in norm al human jejunum, ileum, and colon were investigated. Cytokine mRNA ex pression in IEL and enterocytes was determined by reverse transcriptas e-PCR and IFN-gamma(+) IEL by immunohistochemistry. Polyclonal activat ors were used to study proliferation and IFN-gamma secretion of IEL, a nd an anti-CD3-mediated redirected cytotoxicity assay was used to dete rmine the lytic potential of IEL. Freshly isolated IEL at all three gu t levels expressed mRNA for IL-1 beta, IL-2, IL-8, IFN-gamma, and TNF- alpha. Approximately 10% of IEL produced IFN-gamma, suggesting that IE L are immunologically active in vivo; performing similar functions alo ng the intestine. IEL could be stimulated further in vitro to express IL-10, TNF-beta, and TGF-beta 1, while no Th2-type cytokines were indu ced, suggesting suppressive and cytolytic functions for IEL. All three jejunal IEL subpopulations (CD4(-)CD8(-)TCR-gamma delta(+), CD4(+)TCR -alpha beta(+), CD8(+)TCR-alpha beta(+)) expressed the same four cytok ines, IL-2, IL-8, IFN-gamma, and TNF-alpha, indicating that CD4(+)TCR- alpha beta(+) IEL are Th1 cells and that TCR-gamma delta(+) IEL and CD 8(+)TCR-alpha beta(+) IEL include cytotoxic effector cells. Indeed, fr eshly isolated jejunal IEL displayed cytolytic activity. IEL were indu ced to proliferation by anti-CD3/TCR complex mAbs and leukoagglutinin, but not by Con A. There was no correlation between the magnitude of t he proliferative response and the amounts of secreted IFN-gamma. Enter ocytes expressed IL-1 beta and IL-8, and sometimes TNF-alpha. Although jejunal enterocytes express HLA-DR and hsp60, Ag presentation by thes e cells may induce anergy since their cytokine profile is different fr om that of classical APCs.