T cell receptor-triggered activation of intraepithelial lymphocytes in vitro |
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Authors: | Gramzinski Robert A; Adams Earl; Gross Jane A; Goodman Thomas G; Allison James P; Lefrancois Leo |
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Institution: | 1 Departments of Cell Biology, The Upjohn Company Kalamazoo, Ml 49001, USA
2 Cancer Research and Infectious Diseases, The Upjohn Company Kalamazoo, Ml 49001, USA
3 Department of Molecular and Cell Biology, University of California Berkeley, CA 94720, USA
4 Department of Medicine, University of Connecticut Health Center Farmington, CT 06030, USA
5Present address: AFRC Institute for Animal Health Compton, Berkshire, RG16 0NN, UK |
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Abstract: | Intraepithelial lymphocytes (IEL) of the mouse small intestinewere examined for their potential to respond to TCR signallingin vitro. Purified IEL subsets were activated using mAbs specificfor CD3, TCR ßor TCR &. Thy-1+IEL, regardless ofTCR type, proliferated equally well in response to anti-TCRmAb with or without exogenous IL-2. In contrast, Thy-1–TCR![{alpha}](http://intimm.oxfordjournals.org/math/alpha.gif) , CD8 – IEL required exogenous IL-2 for proliferation.No such requirement was observed for Thy-1– TCR & IELproliferation. IEL proliferation in the absence of added IL-2was due to an IL-2 secretion/IL-2 receptor (IL-2R) autocrinepathway, since mAbs specific for IL-2 and IL-2R inhibited IELproliferation. Thy-1+ CD8ß– CD4+CD8+ IEL wereunresponsive to TCR-induced proliferation but exhibited highlevels of cytolytic activity upon TCR-triggerlng. Thy-1–non-cytolytic IEL were induced to express Thy-1 and cytolytlcactivity following activation in vitro. In addition, the involvementof the co-stimulatory molecule CD28 in IEL activation was tested.CD28 was weakly expressed by fresh IEL and anti-CD28 mAb hadno effect on TCR-triggered proliferation. However, anti-TCRstimulation increased CD28 expression on a subset of TCR ßIEL and the addition of anti-CD28 mAb resulted in increasedIL-2 production, but not in increased proliferation. Our resultsindicate that IEL, including the purported extrathymlc CD8ß–subset, can respond to TCR-driven signals via proliferationand/or cytolytlc activity. |
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Keywords: | intraepithelial lymphocyte CD28 T cell receptor intestine |
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