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Circulating CD8 T Lymphocytes in Human Immunodeficiency
Virus-Infected Individuals Have Impaired Function and Downmodulate
CD3 , the Signaling Chain of the T-Cell Receptor Complex
Linda A. Trimble and
Judy Lieberman
From The Center for Blood Research, Harvard Medical School, Boston,
MA.
Although human immunodeficiency virus (HIV)-infected subjects
without acquired immunodeficiency syndrome have a high frequency of
HIV-specific CD8 T lymphocytes, freshly isolated lymphocytes frequently
lack detectable HIV-specific cytotoxicity. However, this effector
function becomes readily apparent after overnight culture. To
investigate reasons for T-cell dysfunction, we analyzed T-cell
expression of the cytolytic protease granzyme A and of CD3 , the
signaling component of the T-cell receptor complex. An increased
proportion of CD4 and CD8 T cells from HIV-infected donors contain
granzyme A, consistent with the known increased frequency of activated
T cells. In 28 HIV-infected donors with mild to advanced
immunodeficiency, a substantial fraction of circulating T cells
downmodulated CD3 (fraction of T cells expressing CD3, 0.74 ± 0.16 v 1.01 ± 0.07 in healthy donors; P < .0000005). CD3 expression is downregulated more severely in CD8 than
CD4 T cells, decreases early in infection, and correlates with
declining CD4 counts and disease stage. CD3 expression increases
over 6 to 16 hours of culture in an interleukin-2-dependent manner,
coincident with restoration of viral-specific cytotoxicity. Impaired
T-cell receptor signaling may help explain why HIV-specific cytotoxic T
lymphocytes fail to control HIV replication.
Blood, Vol. 91 No. 2 (January 15), 1998:
pp. 585-594
© 1998 by The American Society of Hematology.
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