The Journal of Experimental Medicine
Fluorescence In Vivo Endomicroscopy
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Published online 12 June 2000.
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© The Rockefeller University Press, 0022-1007/2000/6/2031/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 12, June 19, 2000 2031-2038


Original Article

Expression of Bcl-XL Restores Cell Survival, but Not Proliferation and Effector Differentiation, in CD28-deficient T Lymphocytes

A. Maria Dahla, Christoph Kleinb, Pietro G. Andresa, Cheryl A. Londona, Michael P. Lodgea, Richard C. Mulliganb, and Abul K. Abbasa
a Immunology Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
b Howard Hughes Medical Institute, Department of Genetics, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02215

Correspondence to: Abul K. Abbas, Department of Pathology, University of California at San Francisco, S-534, 513 Parnassus Ave., San Francisco, CA 94143. Tel:415-514-0681 Fax:415-514-0841 E-mail:aabbas{at}ucsf.itsa.edu.

Lymphocytes deficient in the T cell costimulatory molecule CD28 exhibit defects in cell survival, clonal expansion, and differentiation into effector cells. It is known that CD28-mediated signaling results in the upregulation of the Bcl family member Bcl-XL. To investigate the role that Bcl-XL plays in the various functions of CD28, we expressed Bcl-XL in CD28-deficient primary T lymphocytes using retrovirus-mediated gene transfer. T cells were activated in vitro and infected with Bcl-XL or control retroviruses; this method allows gene expression in activated, cycling cells. Expression of Bcl-XL in naive T cells was achieved by reconstitution of the immune system of lethally irradiated recipient mice with retrovirus-infected purified bone marrow stem cells from CD28-/- or wild-type donor mice. Our studies demonstrate that Bcl-XL prolongs the survival of CD28-/- T cells but does not restore normal proliferation or effector cell development. These results indicate that the various functions of CD28 can be dissociated, and provide an experimental approach for testing the roles of downstream signals in the functions of cellular receptors such as CD28.

Key Words: CD4+ T lymphocyte, retrovirus-mediated gene transfer, bone marrow reconstitution, costimulation, Th2 differentiation


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