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Departments of Cancer Biology and Medicine and Abramson Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104
T cells require continual presence of extrinsic signals from their
in vivo microenvironment to maintain viability. T cells removed from
these signals and placed in tissue culture atrophied and died in a
caspase-independent manner. Atrophy was characterized by smaller cell
sizes, delayed mitogenic responses, and decreased glycolytic rate.
Bcl-2 expression remained constant in vitro despite ongoing cell death,
indicating that endogenous Bcl-2 expression is insufficient to explain
the life span and size control of lymphocytes in vivo and that
cell-extrinsic signals provided may be required to maintain both cell
viability and size in vivo. One such signal, IL-7, was found to
maintain both the size and survival of neglected T cells in vitro. IL-7
was not unique, because the common 
-chain cytokines IL-2, IL-4, and
IL-15, as well as the gp130 cytokine IL-6, also promoted both T cell
survival and size maintenance. IL-7 did not induce resting T cells to
proliferate. Instead, IL-7 stimulated neglected T cells to maintain
their metabolic rate at levels comparable to freshly isolated cells.
The survival and trophic effects of IL-7 could be separated because
IL-7 was able to promote up-regulation of Bcl-2 and maintain cell
viability independent of phosphatidylinositol 3-kinase and mammalian
target of rapamycin activity but was unable to prevent cellular atrophy
when phosphatidylinositol 3-kinase and mammalian target of rapamycin
were inhibited. These data demonstrate that T cells require the
continuous presence of extrinsic signals not only to survive but also
to maintain their size, metabolic activity, and the ability to respond
rapidly to mitogenic signals.
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A. Audige, E. Schlaepfer, H. Joller, and R. F. Speck Uncoupled Anti-HIV and Immune-Enhancing Effects when Combining IFN-{alpha} and IL-7 J. Immunol., September 15, 2005; 175(6): 3724 - 3736. [Abstract] [Full Text] [PDF]
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 R. G.B. Bonegio, R. Fuhro, Z. Wang, C. R. Valeri, C. Andry, D. J. Salant, and W. Lieberthal Rapamycin Ameliorates Proteinuria-Associated Tubulointerstitial Inflammation and Fibrosis in Experimental Membranous Nephropathy J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2063 - 2072. [Abstract] [Full Text] [PDF]
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T. J. Fry and C. L. Mackall The Many Faces of IL-7: From Lymphopoiesis to Peripheral T Cell Maintenance J. Immunol., June 1, 2005; 174(11): 6571 - 6576. [Abstract] [Full Text] [PDF]
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T. Zhang, R. Somasundaram, K. Berencsi, L. Caputo, P. Rani, D. Guerry, E. Furth, B. J. Rollins, M. Putt, P. Gimotty, et al. CXC Chemokine Ligand 12 (Stromal Cell-Derived Factor 1{alpha}) and CXCR4-Dependent Migration of CTLs toward Melanoma Cells in Organotypic Culture J. Immunol., May 1, 2005; 174(9): 5856 - 5863. [Abstract] [Full Text] [PDF]
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B. Vasir, D. Avigan, Z. Wu, K. Crawford, S. Turnquist, J. Ren, and D. Kufe Dendritic Cells Induce MUC1 Expression and Polarization on Human T Cells by an IL-7-Dependent Mechanism J. Immunol., February 15, 2005; 174(4): 2376 - 2386. [Abstract] [Full Text] [PDF]
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J. Higgins, J. A. Metcalf, R. A. Stevens, M. Baseler, M. C. Nason, H. C. Lane, and I. Sereti Effects of Lymphocyte Isolation and Timing of Processing on Detection of CD127 Expression on T Cells in Human Immunodeficiency Virus-Infected Patients Clin. Vaccine Immunol., January 1, 2005; 12(1): 228 - 230. [Abstract] [Full Text] [PDF]
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D. J. Powell Jr, M. E. Dudley, P. F. Robbins, and S. A. Rosenberg Transition of late-stage effector T cells to CD27+ CD28+ tumor-reactive effector memory T cells in humans after adoptive cell transfer therapy Blood, January 1, 2005; 105(1): 241 - 250. [Abstract] [Full Text] [PDF]
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J. T. Barata, A. Silva, J. G. Brandao, L. M. Nadler, A. A. Cardoso, and V. A. Boussiotis Activation of PI3K Is Indispensable for Interleukin 7-mediated Viability, Proliferation, Glucose Use, and Growth of T Cell Acute Lymphoblastic Leukemia Cells J. Exp. Med., September 7, 2004; 200(5): 659 - 669. [Abstract] [Full Text] [PDF]
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K. A. Frauwirth and C. B. Thompson Regulation of T Lymphocyte Metabolism J. Immunol., April 15, 2004; 172(8): 4661 - 4665. [Abstract] [Full Text] [PDF]
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C. Petrovas, Y. M. Mueller, I. D. Dimitriou, P. M. Bojczuk, K. C. Mounzer, J. Witek, J. D. Altman, and P. D. Katsikis HIV-Specific CD8+ T Cells Exhibit Markedly Reduced Levels of Bcl-2 and Bcl-xL J. Immunol., April 1, 2004; 172(7): 4444 - 4453. [Abstract] [Full Text] [PDF]
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M. Gendelman, T. Hecht, B. Logan, S. Vodanovic-Jankovic, R. Komorowski, and W. R. Drobyski Host Conditioning Is a Primary Determinant in Modulating the Effect of IL-7 on Murine Graft-versus-Host Disease J. Immunol., March 1, 2004; 172(5): 3328 - 3336. [Abstract] [Full Text] [PDF]
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R. M. Kondrack, J. Harbertson, J. T. Tan, M. E. McBreen, C. D. Surh, and L. M. Bradley Interleukin 7 Regulates the Survival and Generation of Memory CD4 Cells J. Exp. Med., December 15, 2003; 198(12): 1797 - 1806. [Abstract] [Full Text] [PDF]
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J. Li, G. Huston, and S. L. Swain IL-7 Promotes the Transition of CD4 Effectors to Persistent Memory Cells J. Exp. Med., December 15, 2003; 198(12): 1807 - 1815. [Abstract] [Full Text] [PDF]
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J.-F. Poulin, M. Sylvestre, P. Champagne, M.-L. Dion, N. Kettaf, A. Dumont, M. Lainesse, P. Fontaine, D.-C. Roy, C. Perreault, et al. Evidence for adequate thymic function but impaired naive T-cell survival following allogeneic hematopoietic stem cell transplantation in the absence of chronic graft-versus-host disease Blood, December 15, 2003; 102(13): 4600 - 4607. [Abstract] [Full Text] [PDF]
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M. A. Burchill, C. A. Goetz, M. Prlic, J. J. O'Neil, I. R. Harmon, S. J. Bensinger, L. A. Turka, P. Brennan, S. C. Jameson, and M. A. Farrar Distinct Effects of STAT5 Activation on CD4+ and CD8+ T Cell Homeostasis: Development of CD4+CD25+ Regulatory T Cells versus CD8+ Memory T Cells J. Immunol., December 1, 2003; 171(11): 5853 - 5864. [Abstract] [Full Text] [PDF]
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 B. T. Endrizzi and S. C. Jameson Differential role for IL-7 in inducing lung Kruppel-like factor (Kruppel-like factor 2) expression by naive versus activated T cells Int. Immunol., November 1, 2003; 15(11): 1341 - 1348. [Abstract] [Full Text] [PDF]
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E. Verhoeyen, V. Dardalhon, O. Ducrey-Rundquist, D. Trono, N. Taylor, and F.-L. Cosset IL-7 surface-engineered lentiviral vectors promote survival and efficient gene transfer in resting primary T lymphocytes Blood, March 15, 2003; 101(6): 2167 - 2174. [Abstract] [Full Text] [PDF]
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 M. J. Lindemann, M. Benczik, and S. L. Gaffen Anti-apoptotic Signaling by the Interleukin-2 Receptor Reveals a Function for Cytoplasmic Tyrosine Residues within the Common gamma (gamma c) Receptor Subunit J. Biol. Chem., March 14, 2003; 278(12): 10239 - 10249. [Abstract] [Full Text] [PDF]
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Q. Yu, B. Erman, A. Bhandoola, S. O. Sharrow, and A. Singer In Vitro Evidence That Cytokine Receptor Signals Are Required for Differentiation of Double Positive Thymocytes into Functionally Mature CD8+ T Cells J. Exp. Med., February 17, 2003; 197(4): 475 - 487. [Abstract] [Full Text] [PDF]
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X. Liu, A. Adams, K. F. Wildt, B. Aronow, L. Feigenbaum, and R. Bosselut Restricting Zap70 Expression to CD4+CD8+ Thymocytes Reveals a T Cell Receptor-dependent Proofreading Mechanism Controlling the Completion of Positive Selection J. Exp. Med., February 3, 2003; 197(3): 363 - 373. [Abstract] [Full Text] [PDF]
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