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*
Department of Immunology, The Royal Free Hospital School of Medicine, London, United Kingdom;
Imperial Cancer Research Fund Tumour Immunology Unit and Department of Oncology and Sexually Transmitted Diseases, University College London Medical School, London, United Kingdom; and
Department of Rheumatology, Birmingham University Medical School, Birmingham, United Kingdom
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 
-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.
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C. M. Steffens, E. Z. Managlia, A. Landay, and L. Al-Harthi Interleukin-7-treated naive T cells can be productively infected by T-cell-adapted and primary isolates of human immunodeficiency virus 1 Blood, May 1, 2002; 99(9): 3310 - 3318. [Abstract] [Full Text] [PDF]
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Y. Okamoto, D. C. Douek, R. D. McFarland, and R. A. Koup Effects of exogenous interleukin-7 on human thymus function Blood, April 15, 2002; 99(8): 2851 - 2858. [Abstract] [Full Text] [PDF]
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M. Maurice, E. Verhoeyen, P. Salmon, D. Trono, S. J. Russell, and F.-L. Cosset Efficient gene transfer into human primary blood lymphocytes by surface-engineered lentiviral vectors that display a T cell-activating polypeptide Blood, April 1, 2002; 99(7): 2342 - 2350. [Abstract] [Full Text] [PDF]
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S. Kimmig, G. K. Przybylski, C. A. Schmidt, K. Laurisch, B. Mowes, A. Radbruch, and A. Thiel Two Subsets of Naive T Helper Cells with Distinct T Cell Receptor Excision Circle Content in Human Adult Peripheral Blood J. Exp. Med., March 18, 2002; 195(6): 789 - 794. [Abstract] [Full Text] [PDF]
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O. Alpdogan, C. Schmaltz, S. J. Muriglan, B. J. Kappel, M.-A. Perales, J. A. Rotolo, J. A. Halm, B. E. Rich, and M. R. M. van den Brink Administration of interleukin-7 after allogeneic bone marrow transplantation improves immune reconstitution without aggravating graft-versus-host disease Blood, October 1, 2001; 98(7): 2256 - 2265. [Abstract] [Full Text] [PDF]
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J. Hassan and D. J. Reen Human Recent Thymic Emigrants-Identification, Expansion, And Survival Characteristics J. Immunol., August 15, 2001; 167(4): 1970 - 1976. [Abstract] [Full Text] [PDF]
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 V. Dardalhon, S. Jaleco, S. Kinet, B. Herpers, M. Steinberg, C. Ferrand, D. Froger, C. Leveau, P. Tiberghien, P. Charneau, et al. IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4+ T cells PNAS, July 19, 2001; (2001) 161272698. [Abstract] [Full Text] [PDF]
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 L. Vivien, C. Benoist, and D. Mathis T lymphocytes need IL-7 but not IL-4 or IL-6 to survive in vivo Int. Immunol., June 1, 2001; 13(6): 763 - 768. [Abstract] [Full Text] [PDF]
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T. J. Fry, B. L. Christensen, K. L. Komschlies, R. E. Gress, and C. L. Mackall Interleukin-7 restores immunity in athymic T-cell-depleted hosts Blood, March 15, 2001; 97(6): 1525 - 1533. [Abstract] [Full Text] [PDF]
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L. A. Geiselhart, C. A. Humphries, T. A. Gregorio, S. Mou, J. Subleski, and K. L. Komschlies IL-7 Administration Alters the CD4:CD8 Ratio, Increases T Cell Numbers, and Increases T Cell Function in the Absence of Activation J. Immunol., March 1, 2001; 166(5): 3019 - 3027. [Abstract] [Full Text] [PDF]
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K. Weinberg, B. R. Blazar, J. E. Wagner, E. Agura, B. J. Hill, M. Smogorzewska, R. A. Koup, M. R. Betts, R. H. Collins, and D. C. Douek Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation Blood, March 1, 2001; 97(5): 1458 - 1466. [Abstract] [Full Text] [PDF]
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S. Gozalo-Sanmillan, J. M. McNally, M. Y. Lin, C. A. Chambers, and L. J. Berg Cutting Edge: Two Distinct Mechanisms Lead to Impaired T Cell Homeostasis in Janus Kinase 3- and CTLA-4-Deficient Mice J. Immunol., January 15, 2001; 166(2): 727 - 730. [Abstract] [Full Text] [PDF]
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E. C. Tsark, M. A. Dao, X. Wang, K. Weinberg, and J. A. Nolta IL-7 Enhances the Responsiveness of Human T Cells That Develop in the Bone Marrow of Athymic Mice J. Immunol., January 1, 2001; 166(1): 170 - 181. [Abstract] [Full Text] [PDF]
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G. Lombardi, P. J. Dunne, D. Scheel-Toellner, T. Sanyal, D. Pilling, L. S. Taams, P. Life, J. M. Lord, M. Salmon, and A. N. Akbar Type 1 IFN Maintains the Survival of Anergic CD4+ T Cells J. Immunol., October 1, 2000; 165(7): 3782 - 3789. [Abstract] [Full Text] [PDF]
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V. Dardalhon, S. Jaleco, C. Rebouissou, C. Ferrand, N. Skander, L. Swainson, P. Tiberghien, H. Spits, N. Noraz, and N. Taylor Highly efficient gene transfer in naive human T cells with a murine leukemia virus-based vector Blood, August 1, 2000; 96(3): 885 - 893. [Abstract] [Full Text] [PDF]
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N. C. Matthews, M. Wadhwa, C. Bird, F. E. Borras, and C. V. Navarrete Sustained Expression of CD154 (CD40L) and Proinflammatory Cytokine Production by Alloantigen-Stimulated Umbilical Cord Blood T Cells J. Immunol., June 15, 2000; 164(12): 6206 - 6212. [Abstract] [Full Text] [PDF]
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D. Unutmaz, V. N. KewalRamani, S. Marmon, and D. R. Littman Cytokine Signals Are Sufficient for HIV-1 Infection of Resting Human T Lymphocytes J. Exp. Med., June 7, 1999; 189(11): 1735 - 1746. [Abstract] [Full Text] [PDF]
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M. K. Maini, M. V. D. Soares, C. F. Zilch, A. N. Akbar, and P. C. L. Beverley Virus-Induced CD8+ T Cell Clonal Expansion Is Associated with Telomerase Up-Regulation and Telomere Length Preservation: A Mechanism for Rescue from Replicative Senescence J. Immunol., April 15, 1999; 162(8): 4521 - 4526. [Abstract] [Full Text] [PDF]
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V. Dardalhon, S. Jaleco, S. Kinet, B. Herpers, M. Steinberg, C. Ferrand, D. Froger, C. Leveau, P. Tiberghien, P. Charneau, et al. IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4+ T cells PNAS, July 31, 2001; 98(16): 9277 - 9282. [Abstract] [Full Text] [PDF]
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