This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Singh, R. K. Articles by Talmadge, J. E. Search for Related Content PubMed PubMed Citation Articles by Singh, R. K. Articles by Talmadge, J. E.

Fas-FasL-mediated CD4+ T-Cell Apoptosis following Stem Cell Transplantation¹

Departments of Pathology and Microbiology [R. K. S., M. L. V., S. B., K. I., A. G. A., J. E. T.] and Internal Medicine-Oncology/Hematology [E. R., S. T.], University of Nebraska Medical Center, Omaha, Nebraska 68198

We report the preferential expression of Fas on CD4⁺ T cells and Fas ligand (FasL) on monocytes and their potential role in the selective loss of CD4⁺ T cells in breast cancer patients undergoing high-dose chemotherapy and peripheral blood stem cell transplantation (PSCT). A high frequency of apoptotic CD4⁺ T cells (28–51%) is observed during the first 100 days after PSCT concomitant with a significant increase in monocyte frequency and FasL expression (11.6–23%) on monocytes. The preferential expression of Fas on CD4⁺ T cells (73–92%) in the peripheral blood (PB) of these patients is associated with a significantly higher frequency of CD4⁺ T-cell apoptosis compared with CD8⁺ T cells (28–47%) and CD4⁺ T cells (46 ± 5.7%) in normal PB. These data suggest that "primed" Fas⁺ CD4⁺ lymphocytes interact with activated monocytes that express FasL, resulting in apoptosis, leading to deletion of CD4⁺ T cells, an inversion in the CD4:CD8 T-cell ratio, and immune dysfunction. The prevention of CD4⁺ T-cell apoptosis and improved immune reconstitution by the manipulation of PB stem cell products, blockade of Fas-FasL interactions, or cytokine support after transplantation may be important adjuvant immunotherapeutic strategies in patients undergoing high-dose chemotherapy and PSCT.

This article has been cited by other articles:

				L. Frydelund-Larsen, M. Penkowa, T. Akerstrom, A. Zankari, S. Nielsen, and B. K. Pedersen Muscle: Exercise induces interleukin-8 receptor (CXCR2) expression in human skeletal muscle Exp Physiol, January 1, 2007; 92(1): 233 - 240. [Abstract] [Full Text] [PDF]

				S. Rutella, F. Zavala, S. Danese, H. Kared, and G. Leone Granulocyte Colony-Stimulating Factor: A Novel Mediator of T Cell Tolerance J. Immunol., December 1, 2005; 175(11): 7085 - 7091. [Abstract] [Full Text] [PDF]

				P. A. Muraro, D. C. Douek, A. Packer, K. Chung, F. J. Guenaga, R. Cassiani-Ingoni, C. Campbell, S. Memon, J. W. Nagle, F. T. Hakim, et al. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients J. Exp. Med., March 7, 2005; 201(5): 805 - 816. [Abstract] [Full Text] [PDF]

				R. K. Gilroy, P. F. Coccia, J. E. Talmadge, L. I. Hatcher, S. J. Pirruccello, B. W. Shaw Jr, R. J. Rubocki, D. L. Sudan, A. N. Langnas, and S. P. Horslen Donor immune reconstitution after liver-small bowel transplantation for multiple intestinal atresia with immunodeficiency Blood, February 1, 2004; 103(3): 1171 - 1174. [Abstract] [Full Text] [PDF]

				A. Heitger, P. Winklehner, P. Obexer, J. Eder, C. Zelle-Rieser, G. Kropshofer, M. Thurnher, and W. Holter Defective T-helper cell function after T-cell-depleting therapy affecting naive and memory populations Blood, May 13, 2002; 99(11): 4053 - 4062. [Abstract] [Full Text] [PDF]