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Expression of the CD8  -Heterodimer on CD8+ T
Lymphocytes in Peripheral Blood Lymphocytes of Human Immunodeficiency
Virus and Human Immunodeficiency Virus+
Individuals
Jörn E. Schmitz,
Meryl A. Forman,
Michelle A. Lifton,
Orlando Concepción Jr,
Keith A. Reimann,
Clyde S. Crumpacker,
John F. Daley,
Rebecca S. Gelman, and
Norman L. Letvin
From the Divisions of Viral Pathogenesis and Infectious Diseases,
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard
Medical School, Boston, MA; Coulter Corporation, Miami, FL; and the
Division of Hematologic Malignancies, the Department of Medicine and
Statistical and Data Analysis Center, the Division of Biostatistics and
Epidemiology, Harvard Medical School, Dana-Farber Cancer Institute,
Boston, MA.
CD8+ T lymphocytes play a pivotal role in controlling
human immunodeficiency virus (HIV)-1 replication in vivo. We have
performed four-color flow cytometric analysis of CD8+
peripheral blood lymphocytes (PBL) from 21 HIV-1 seronegative and 103 seropositive individuals to explore the phenotypic heterogeneity of
CD8 -chain expression on CD8+ T lymphocytes and to
clarify how its expression on CD8+ T lymphocytes may
relate to acquired immunodeficiency syndrome (AIDS)
clinical progression. We showed that the single monoclonal antibody
(MoAb) 2ST8-5H7, directed against the CD8 -heterodimer, identifies
CD8+ T lymphocytes as effectively as the conventional
combination of anti-CD3 and anti-CD8 antibodies. However, we
detected a significantly lower mean fluorescence (MF) of anti-CD8
staining on PBL from HIV-1 seropositive donors as compared with
seronegative donors. In fact, CD8+ T lymphocytes from
HIV-1-infected individuals with the lowest CD4 counts showed the
lowest levels of CD8 MF. To explore further this change in
CD8 expression, we assessed the expression of 14 different cell
surface molecules on CD8+ T lymphocytes of PBL from
11 HIV-1 seronegative and 22 HIV-1 seropositive individuals. The MF of
anti-CD8 staining was significantly reduced on CD8+
T lymphocyte subsets that showed immunophenotypic evidence of activation. The subset of lymphocytes expressing low levels of CD8 expressed higher levels of activation, adhesion, and
cytotoxic-associated molecules and was predominantly
CD45RO+ and CD28 . Finally, we monitored
the expression of the CD8-heterodimer on PBL of eight
HIV-1-infected individuals over a 16-week period after the initiation
of highly active antiretroviral therapy (HAART), including zidovudine
(ZDV), lamivudine (3TC), and indinavir (IDV), and found a significant
increase in the expression of the CD8-heterodimer. These results
suggest that antibodies recognizing the CD8-heterodimer are
useful tools to specifically identify CD8+ T lymphocytes.
Moreover, the quantitative monitoring of CD8 expression allows
the detection of discrete CD8+ T lymphocyte subsets and
may be useful for assessing the immune status of individuals infected
with HIV-1.
Blood, Vol. 92 No. 1 (July 1), 1998:
pp. 198-206
© 1998 by The American Society of Hematology.
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