Hematopoietic cell protein-tyrosine phosphatase-deficient motheaten mice exhibit T cell apoptosis defect.
We previously demonstrated that hematopoietic cell protein-tyrosine phosphatase is one of the molecules that can transduce Fas-mediated apoptosis signals in lymphoid cells. The present study analyzed the effect of defective Fas signaling on the T cell phenotype and apoptosis function in hematopoietic cell protein-tyrosine phosphatase-deficient motheaten mice. Viable motheaten (me(v)/me(v)) mice exhibited increased T cell proliferation and defective activation-induced apoptosis of Fas+ T cells in the lymph node, which was not ascribed to defective Fas ligand function. Furthermore, the Fas-mediated apoptosis defect in activated T cells from me(v)/me(v) mice was confirmed by their resistance to anti-Fas-induced apoptosis. No protein tyrosine dephosphorylation signal was delivered after anti-Fas cross-linking in the lymph node cells of me(v)/me(v) mice as revealed by 32Pi labeling of protein phosphatase substrates. The defective activation-induced apoptosis of Fas+ T cells in me(v)/me(v) mice led to lymphadenopathy with an accumulation of CD4- CD8- B220+ CD3+ T cells. Pneumonitis in me(v)/me(v) mice was associated with infiltration of cycling T cells detected by bromodeoxyuridine uptake in vivo. Thus, T cells from me(v)/me(v) mice are resistant to Fas-mediated apoptosis which results in lymphoproliferative disease and tissue infiltration.
Su
X
X
Department of Medicine, the University of Alabama at Birmingham, AL 35294, USA.
Zhou
T
T
Yang
P A
PA
Wang
Z
Z
Mountz
J D
JD
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology; D006413:Hematopoietic System / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000201:enzymology / Q000209:etiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010641:Phenotype; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D019014:fas Receptor / Q000378:metabolism
D019014:fas Receptor; D017027:Protein Tyrosine Phosphatases