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Blood, 1 July 2001, Vol. 98, No. 1, pp. 156-164
IMMUNOBIOLOGY
CD8 T cells specific for human immunodeficiency virus,
Epstein-Barr virus, and cytomegalovirus lack molecules for homing to
lymphoid sites of infection
Gang Chen,
Premlata Shankar,
Christoph Lange,
Hernan Valdez,
Paul R. Skolnik,
Lijun Wu,
N. Manjunath, and
Judy Lieberman
From the Center for Blood Research and Department of
Pediatrics, Harvard Medical School, Boston, MA; Division of Infectious
Diseases, Department of Medicine, University Hospitals of Cleveland,
Case Western Reserve University, Cleveland, OH; Division of Infectious
Diseases and Geographic Medicine, Department of Medicine, New
England Medical Center, Tufts University School of Medicine, Boston,
MA; and Millennium Pharmaceuticals, Inc, Cambridge, MA.
CD8 T cells are classified as naïve, effector, or memory
cells on the basis of CD45RA, CD62L, and CCR7 expression. Sequential engagement of cell-surface CD62L and CCR7 receptors is required for
efficient trafficking to lymphoid tissue by means of high endothelial
venules. Naïve CD8 T cells are
CCR7+CD62L+ CD45RA+, whereas
long-term memory cells are
CCR7+CD62L+CD45RA . Effector
cytotoxic T cells are thought to be
CCR7 CD45RA+. The distribution of CD8 subsets
and cytolytic protein expression in healthy donors and donors
seropositive for human immunodeficiency virus (HIV) were compared. In
HIV-infected subjects, CCR7 CD8 T cells expanded at the
expense of naïve and long-term memory cells. In both healthy
donors and HIV-infected donors, CCR7+ CD8 T cells were
uniformly negative for perforin. In all subsets, perforin and granzyme
A were not coordinately expressed, with perforin expression being more
tightly regulated. The properties of CD8 T cells specific for
cytomegalovirus, Epstein-Barr virus (EBV), and HIV were studied by
staining with major histocompatibility complex peptide tetramers.
Antigen-specific cells for chronic infections with these viruses were
uniformly CCR7 and predominantly CD62L . In
2 HIV-seropositive donors, 3- to 4-fold fewer EBV-tetramer-positive cells were present in lymph nodes compared with blood. Antigen-specific CD8 T cells are therefore preferentially excluded from lymphoid sites,
even when infection is primarily in lymphoid tissue. This may protect
lymphoid tissues from immunopathological changes but compromise immune
defense against viruses, such as HIV and EBV, that target lymphocytes.
HIV-specific CD8 T cells do not express CD45RA, whereas EBV- and
CMV-specific CD8 T cells are heterogeneous in CD45RA+
expression. Lack of CD45RA expression may indicate incomplete differentiation of HIV-specific CD8 T cells to cytotoxic T cells.

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