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Publication : Differential requirements of CD45 protein tyrosine phosphatase for cytolytic activities and intrathymic and extrathymic development of intestinal intraepithelial lymphocytes.

First Author  Yada S Year  1998
Journal  J Immunol Volume  161
Issue  5 Pages  2208-16
PubMed ID  9725213 Mgi Jnum  J:111646
Mgi Id  MGI:3654612 Doi  10.4049/jimmunol.161.5.2208
Citation  Yada S, et al. (1998) Differential requirements of CD45 protein tyrosine phosphatase for cytolytic activities and intrathymic and extrathymic development of intestinal intraepithelial lymphocytes. J Immunol 161(5):2208-16
abstractText  CD45 is a transmembrane protein tyrosine phosphatase essential for Ag receptor-mediated signaling in both T and B cells. In this study we investigated roles of CD45 in development and cytolytic activities of murine intestinal intraepithelial lymphocytes (i-IEL) using CD45 exon 6 knockout (CD45-/-) mice. Interestingly, the total cell number of i-IEL was significantly reduced in CD45-/-mice during aging (10-20 wk of age), whereas the i-IEL number was normally increased in the wild-type littermates. Especially, the number of gamma(delta)TCR+ i-IEL decreased markedly in CD45-/- mice during aging. The i-IEL in CD45-/- mice were more susceptible to in vitro spontaneous apoptosis than the normal i-IEL, implying that CD45 is required for maintenance of the cellularity of i-IEL. Results from in vivo analyses of the extrathymic and intrathymic development of i-IEL suggested that CD45-mediated signaling is required for the intrathymic, but not the extrathymic, development of i-IEL. Moreover, the whole i-IEL from CD45-/- mice showed a significantly reduced cytolytic activity, and the residual cytolytic activity was completely diminished by depleting CD45+ i-IEL, suggesting that CD45 is indispensable for the TCR-mediated cytolytic activity of i-IEL. Furthermore, we found differential contributions of CD45 and p56lck to development and induction of cytolytic activities of i-IEL.
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