IL-7-dependent extrathymic expansion of CD45RA+ T cells enables preservation of a naive repertoire

J Immunol. 1998 Dec 1;161(11):5909-17.


We have investigated the regulation of adult and cord blood CD45RA+ T cell proliferation and apoptosis to identify factors that may control the naive T cell pool. Cord CD45RA+ T cells were highly susceptible to spontaneous apoptosis as compared with CD45RA+ T cells from adults. Apoptosis was prevented by the addition of IL-2, IL-4, IL-7, and IL-15 which signal via the gamma-chain of the IL-2 receptor. IL-7 prevented the decrease in Bcl-2 and Bcl-xL and induced cell cycling in up to 20% of cord T cells after 8 days, resulting in a threefold increase in cord T cell numbers. However, the expanded cells retained a CD45RA+ CD45RO- phenotype. Similar results were obtained with adult CD45RA+ T cells. IL-7-expanded CD45RA+ RO- T cells expressed CD45RO after stimulation through the TCR. Investigations into the regulation of replicative senescence showed that after 12 days in culture with IL-7, cord blood CD45RA+ T cell proliferation resulted in telomere shortening. Nevertheless, IL-7-expanded cord blood T cells still maintained longer telomeres than unstimulated adult T cells. IL-7 but not IL-2 could directly induce high telomerase activity which probably retarded the rate of telomere shortening in cord blood T cells. These results suggest that proliferation induced by IL-7 may be important for extrathymic expansion of neonatal CD45RA+ T cells and may also contribute to the maintenance of the adult CD45RA+ T cell pool.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / pharmacology
  • Apoptosis / immunology
  • CD3 Complex / immunology
  • Cell Division / immunology
  • Cell Survival / immunology
  • Cells, Cultured
  • Cytokines / physiology
  • Enzyme Activation
  • Fetal Blood / cytology
  • Fetal Blood / enzymology
  • Fetal Blood / immunology
  • Homeostasis / immunology*
  • Humans
  • Immunophenotyping
  • Infant, Newborn
  • Interleukin-7 / physiology*
  • Leukocyte Common Antigens / biosynthesis*
  • Lymphocyte Activation
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Receptors, Interleukin-2 / physiology
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / enzymology
  • T-Lymphocyte Subsets / immunology*
  • Telomerase / metabolism
  • Telomere / enzymology
  • Thymus Gland / cytology*
  • Thymus Gland / immunology
  • bcl-X Protein


  • Antibodies, Monoclonal
  • BCL2L1 protein, human
  • CD3 Complex
  • Cytokines
  • Interleukin-7
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Interleukin-2
  • bcl-X Protein
  • Telomerase
  • Leukocyte Common Antigens