Fas ligand-mediated depletion of CD4 and CD8 lymphocytesby monomeric HIV-1-gp120 |
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Authors: | J Uchiyama S Kishi H Yagita S Matsuzaki Y Koga |
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Institution: | (1) Department of Infectious Diseases, Tokai Univesity School of Medicine, Isehara, Kanagawa, Japan, JP;(2) Department of Internal Medicine 3, Tokai University School of Medicine,Isehara, Kanagawa, Japan, JP;(3) Pharmaceutical Basic Research Laboratories, JT Inc., Yokohama, Japan, JP;(4) Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan, JP |
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Abstract: | Summary. In order to determine in what condition and by what mechanism gp 120 can deplete not only CD4 but also CD8 T cells, an in
vitro system was established in which peripheral blood lymphocytes from healthy donors were treated with recombinant gp 120.
We found that gp 120 can deplete both CD4 and CD8 T cells when they have recently been activated and are exposed to IL-2-deficient
conditions. Bioassay of the Fas ligand (FasL) demonstrated augmented expression and release of soluble FasL by CD4 T cells
in the supernatant of this culture. The administration of anti-FasL mAb and anti-Fas mAb, both of which exhibit neutralizing
activity, completely abolished the depletion of these two T cell populations in culture. Based on these findings, we concluded
that FasL depletes Fas antigen expressing CD4 and CD8 T cells by programmed cell death.
Received December 18, 1996 Accepted May 2, 1997 |
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