CD8 T cells specific for human immunodeficiency virus, Epstein-Barr virus, and cytomegalovirus lack molecules for homing to lymphoid sites of infection

Author:

Chen Gang1,Shankar Premlata1,Lange Christoph1,Valdez Hernan1,Skolnik Paul R.1,Wu Lijun1,Manjunath N.1,Lieberman Judy1

Affiliation:

1. 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.

Abstract

Abstract CD8 T cells are classified as naı̈ve, 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. Naı̈ve 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 naı̈ve 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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