Differential requirements of CD45 protein tyrosine phosphatase for cytolytic activities and intrathymic and extrathymic development of intestinal intraepithelial lymphocytes.
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.
Yada
S
S
Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Kishihara
K
K
Kong
Y Y
YY
Nomoto
K
K
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005260:Female; D007413:Intestinal Mucosa / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics; D016131:Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology / Q000276:immunology*
D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases