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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3672-3678.
Prepublished online as a Blood First Edition Paper on August 12, 2004; DOI 10.1182/blood-2004-07-2540.


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IMMUNOBIOLOGY

Expansion of CD7low and CD7negative CD8 T-cell effector subsets in HIV-1 infection: correlation with antigenic load and reversion by antiretroviral treatment

Einar M. Aandahl, Máire F. Quigley, Walter J. Moretto, Markus Moll, Veronica D. Gonzalez, Anders Sönnerborg, Stefan Lindbäck, Frederick M. Hecht, Steven G. Deeks, Michael G. Rosenberg, Douglas F. Nixon, and Johan K. Sandberg

From The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway; the Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; the Gladstone Institute of Virology and Immunology, University of California, San Francisco; the Division for Infectious Diseases, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; the Department of Medicine, University of California, San Francisco; the San Francisco General Hospital, San Francisco, CA; and the Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY.

The antiviral response of CD8 T cells involves the differentiation of naive T cells into distinct types of effector and memory cells, which may be distinguished by the level of CD7 expression. We have investigated CD8 T cells in adults and children infected with HIV-1 to determine the disease relevance of cell subsets defined by CD7. CD8 T cells from patients infected with HIV-1 displayed profound down-modulation of CD7 expression as compared with healthy subjects, with expansion of both CD7low and CD7negative effector subsets. Loss of CD7high cells correlated directly with HIV-1 load and was particularly pronounced in patients with rapid disease progression. CD8 T cells specific for HIV-1, as well as Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were predominantly found in the CD7low effector cell subset. Furthermore, recovery of CD4 counts on antiretroviral therapy was associated with reversion of the skewed CD7 profile in CD8 T cells. Thus, effector CD8 T-cell subsets distinguished by lowered CD7 expression expand in a manner that correlates with the magnitude of HIV-1, EBV, and CMV antigenic challenge and contract in response to successful antiretroviral treatment. The results are discussed in relation to the dual roles of CD7 as a receptor of both costimulation and cell death.


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