IL‐7 promotes the survival and maturation but not differentiation of human post‐thymic CD4+ T cells

This study examines the influence of IL‐7 on post‐thymic CD4+ T cells using cord blood as a model system. Survival of naive cord blood T cells in the presence of IL‐7 alone was significantly prolonged by up‐regulating bcl‐2, thereby preventing apoptosis while maintaining maximal cell viability. Cultures without IL‐7 showed high rates of apoptosis resulting in 50 % cell death by day 5 of culture. Upon phorbol 12‐myristate 13‐acetate + ionomycin stimulation, accumulation of cytoplasmic IL‐2 was similar to that observed in freshly isolated cells, but no IL‐4‐ or IFN‐γ‐positive cells were detected. IL‐7 maintained the naive T cells in a quiescent state expressing the CD45RA antigen. A significant finding was the loss of CD38 antigen expression on the naive cord blood T cells to levels similar to that observed on adult naive T cells. In contrast to the reduced proliferative response of fresh cord blood T cells to anti‐CD2 + CD28 stimulation, the proliferative response of IL‐7‐treated cells was similar to that of adult naive T cells. This study shows that as well as maintaining the naive T cell pool by enhancing cell survival and up‐regulating bcl‐2 expression, IL‐7 also functions as a maturation factor for post‐thymic naive T cells.

[1]  T. Miyoshi‐Akiyama,et al.  Post-thymic maturation of migrating human thymic single-positive T cells: thymic CD1a- CD4+ T cells are more susceptible to anergy induction by toxic shock syndrome toxin-1 than cord blood CD4+ T cells. , 1998, Journal of immunology.

[2]  J. Hassan,et al.  Linkage of protein kinase C‐β activation and intracellular interleukin‐2 accumulation in human naive CD4 T cells , 1997, Immunology.

[3]  H. Ueno,et al.  IL-7 induces proliferation, variable cytokine-producing ability and IL-2 responsiveness in naive CD4+ T-cells from human cord blood. , 1997, Immunology letters.

[4]  P. Marrack,et al.  Interleukin 4 (IL-4) or IL-7 Prevents the Death of Resting T Cells: Stat6 Is Probably Not Required for the Effect of IL-4 , 1997, The Journal of experimental medicine.

[5]  N. Solvason,et al.  The earliest T lineage-committed cells depend on IL-7 for Bcl-2 expression and normal cell cycle progression. , 1997, Immunity.

[6]  I. Weissman,et al.  Bcl-2 Rescues T Lymphopoiesis, but Not B or NK Cell Development, in Common γ Chain–Deficient Mice , 1997 .

[7]  A. Strasser,et al.  Bcl-2 Can Rescue T Lymphocyte Development in Interleukin-7 Receptor–Deficient Mice but Not in Mutant rag-1 −/− Mice , 1997, Cell.

[8]  M. Feldmann,et al.  Interleukin‐7 activates human naive CD4+ cells and primes for interleukin‐4 production , 1997, European journal of immunology.

[9]  B. Adkins,et al.  Naive murine neonatal T cells undergo apoptosis in response to primary stimulation. , 1996, Journal of immunology.

[10]  J. Miyazaki,et al.  Interleukin 7 receptor-deficient mice lack gammadelta T cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[11]  You-Wen He,et al.  Interleukin-7 receptor alpha is essential for the development of gamma delta + T cells, but not natural killer cells , 1996, The Journal of experimental medicine.

[12]  D. Loh,et al.  T-B cell interaction inhibits spontaneous apoptosis of mature lymphocytes in Bcl-2-deficient mice , 1995, The Journal of experimental medicine.

[13]  S. Burdach,et al.  Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine , 1995, The Journal of experimental medicine.

[14]  W. Leonard,et al.  Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain. , 1995, Immunity.

[15]  A. Fischer,et al.  Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[16]  C. Ware,et al.  Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice , 1994, The Journal of experimental medicine.

[17]  S. Nishikawa,et al.  Functional participation of the IL-2 receptor gamma chain in IL-7 receptor complexes. , 1994, Science.

[18]  S. Ziegler,et al.  Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. , 1993, Science.

[19]  S. Nishikawa,et al.  Expression and function of the interleukin 7 receptor in murine lymphocytes. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[20]  S. Wesselborg,et al.  Triggering via the alternative CD2 pathway induces apoptosis in activated human T lymphocytes , 1993, European Journal of Immunology.

[21]  F. Finkelman,et al.  Inhibition of murine B and T lymphopoiesis in vivo by an anti- interleukin 7 monoclonal antibody , 1993, The Journal of experimental medicine.

[22]  F. Takei,et al.  Dual role of IL-7 in the growth and differentiation of immature thymocytes. , 1992, Experimental hematology.

[23]  D. Reen,et al.  Neonatal CD4+ CD45RA+ T cells: precursors of adult CD4+ CD45RA+ T cells? , 1993, Research in immunology.

[24]  I Hannet,et al.  Developmental and maturational changes in human blood lymphocyte subpopulations. , 1992, Immunology today.