CD3ζ and CD28 down-modulation on CD8 T cells during viral infection

Down-modulation of CD3 zeta expression on CD8 T lymphocytes occurs, independently of other T-cell receptor (TCR)-CD3 components, in tumor-infiltrating lymphocytes, human immunodeficiency virus infection, and autoimmune disease. These associations suggest that it might be related to chronic antigenic stimulation. CD3 zeta down-modulation was found, however, in CD8 T cells that in response to acute viral infections. In 3 otherwise healthy donors with acute gastroenteritis, infectious mononucleosis, and Epstein-Barr virus/cytomegalovirus/mononucleosis, 30% to 60% of circulating CD8 T cells had down-modulated CD3 zeta to below the level of detection. The CD3 zeta-T cells were also CD28- but expressed the activation markers HLA-DR and CD57. CD3 zeta-CD28-T cells are effector CTL because they express perforin and produce IFN-gamma, but not IL-2, on activation and contain the viral-specific cytotoxic T lymphocyte (CTL). However, CD35-CD28-T cells generally do not express CD25 after anti-CD3 and anti-CD28 stimulation and are not cytotoxic until they are cultured with IL-2 overnight. Cytotoxicity coincides with the re-expression of CD3 zeta but not CD28, Downmodulation of CD3 zeta acid CD28 on effector CTL may control CTL triggering and proliferation to prevent immunopathogenesis. (C) 2000 by The American Society of Hematology.