Insulin-like growth factor 1 promotes cord blood T cell maturation and inhibits its spontaneous and phytohemagglutinin-induced apoptosis through different mechanisms.
Functional immaturity of neonatal T cells is related to their immature phenotype, with the majority of neonatal T cells of naive (CD45RA+) T cells. The progression of T cells from naive cells to effector cells is dependent on the survival of Ag-specific T cells and their resistance to apoptosis. In this study, we showed for the first time that insulin-like growth factor 1 (IGF-1) converted cord blood CD45RA+ T cells to CD45RO+ T cells and inhibited cord blood T cell apoptosis. We found cord blood T cells stimulated with PHA would result in gradual loss of CD45RA and gain of CD45RO expression. IGF-1 further increased the loss of CD45RA and enhanced CD45RO expression in PHA-stimulated cord blood T cells. In addition, IGF-1 prevented cord blood T cells from spontaneous apoptosis through a mechanism other than Fas/FasL. In PHA-activated cord blood T cells, IGF-1 prevented both naive (CD45RA+) and memory/mature (CD45RO+) T cells from apoptosis. Moreover, cord blood T cells cultured with IGF-1 and PHA had a higher resistance to anti-Fas-induced apoptosis as compared with PHA-activated cord blood T cells. IGF-1 also significantly inhibited PHA-induced Fas expression on cord blood T cells. These results demonstrate that IGF-1 promotes the maturation and maintains the survival of cord blood T cells. Its antiapoptotic effect in PHA-activated cord blood T cells may be mediated through the down-regulation of Fas expression.
Tu
W
W
Department of Pediatrics, Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.
Cheung
P T
PT
Lau
Y L
YL
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D015536:Down-Regulation / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D007156:Immunologic Memory; D007231:Infant, Newborn; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007399:Interphase / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D010835:Phytohemagglutinins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D019014:fas Receptor / Q000096:biosynthesis / Q000276:immunology
D000911:Antibodies, Monoclonal; D016895:Culture Media, Serum-Free; D006131:Growth Inhibitors; D010835:Phytohemagglutinins; D020033:Protein Isoforms; D019014:fas Receptor; D007334:Insulin-Like Growth Factor I; D017493:Leukocyte Common Antigens