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Blood, Vol. 96 No. 3 (August 1), 2000:
pp. 1021-1029
CD3 and CD28 down-modulation on CD8 T cells during
viral infection
Linda A. Trimble,
Lawrence W. Kam,
Rachel S. Friedman,
Zhan Xu, and
Judy Lieberman
From the Center for Blood Research, Harvard Medical School, Boston,
MA.
Down-modulation of CD3 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 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 CD3 to below the level of
detection. The CD3-T cells were also CD28 but expressed the activation markers HLA-DR and CD57. CD3-CD28-
T cells are effector CTL because they
express perforin and produce IFN- , but not IL-2, on activation and
contain the viral-specific cytotoxic T lymphocyte (CTL). However,
CD3-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 but not CD28. Down-modulation of CD3 and CD28 on effector CTL
may control CTL triggering and proliferation to prevent immunopathogenesis.
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