CD3zeta and CD28 down-modulation on CD8 T cells during viral infection.
Down-modulation of CD3zeta 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. CD3zeta down-modulation was found, however, in CD8 T cells that proliferate 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 CD3zeta to below the level of detection. The CD3zeta-T cells were also CD28- but expressed the activation markers HLA-DR and CD57. CD3zeta-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, CD3zeta-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 CD3zeta but not CD28. Down-modulation of CD3zeta and CD28 on effector CTL may control CTL triggering and proliferation to prevent immunopathogenesis.
Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA.
L A
LA
Trimble
L W
LW
Kam
R S
RS
Friedman
Z
Z
Xu
J
J
Lieberman
D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D006801:Humans; D014777:Virus Diseases / Q000276:immunology*
D018106:CD28 Antigens; D017252:CD3 Complex