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      Dramatic Rise in Plasma Viremia after CD8 + T Cell Depletion in Simian Immunodeficiency Virus–infected Macaques

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          Abstract

          To determine the role of CD8 + T cells in controlling simian immunodeficiency virus (SIV) replication in vivo, we examined the effect of depleting this cell population using an anti-CD8 monoclonal antibody, OKT8F. There was on average a 99.9% reduction of CD8 cells in peripheral blood in six infected Macaca mulatta treated with OKT8F. The apparent CD8 depletion started 1 h after antibody administration, and low CD8 levels were maintained until day 8. An increase in plasma viremia of one to three orders of magnitude was observed in five of the six macaques. The injection of a control antibody to an infected macaque did not induce a sustained viral load increase, nor did it significantly reduce the number of CD8 + T cells. These results demonstrate that CD8 cells play a crucial role in suppressing SIV replication in vivo.

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          Most cited references38

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          Molecular beacons: probes that fluoresce upon hybridization.

          We have developed novel nucleic acid probes that recognize and report the presence of specific nucleic acids in homogeneous solutions. These probes undergo a spontaneous fluorogenic conformational change when they hybridize to their targets. Only perfectly complementary targets elicit this response, as hybridization does not occur when the target contains a mismatched nucleotide or a deletion. The probes are particularly suited for monitoring the synthesis of specific nucleic acids in real time. When used in nucleic acid amplification assays, gene detection is homogeneous and sensitive, and can be carried out in a sealed tube. When introduced into living cells, these probes should enable the origin, movement, and fate of specific mRNAs to be traced.
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            Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells.

            Evidence suggests that CD8+ T lymphocytes are involved in the control of human immunodeficiency virus (HIV) infection in vivo, either by cytolytic mechanisms or by the release of HIV-suppressive factors (HIV-SF). The chemokines RANTES, MIP-1 alpha, and MIP-1 beta were identified as the major HIV-SF produced by CD8+ T cells. Two active proteins purified from the culture supernatant of an immortalized CD8+ T cell clone revealed sequence identity with human RANTES and MIP-1 alpha. RANTES, MIP-1 alpha, and MIP-1 beta were released by both immortalized and primary CD8+ T cells. HIV-SF activity produced by these cells was completely blocked by a combination of neutralizing antibodies against RANTES, MIP-1 alpha, and MIP-1 beta. Recombinant human RANTES, MIP-1 alpha, and MIP-1 beta induced a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). These data may have relevance for the prevention and therapy of AIDS.
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              Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome.

              Virologic and immunologic studies were performed on five patients presenting with primary human immunodeficiency virus type 1 (HIV-1) infection. CD8+ cytotoxic T lymphocyte (CTL) precursors specific for cells expressing antigens of HIV-1 Gag, Pol, and Env were detected at or within 3 weeks of presentation in four of the five patients and were detected in all five patients by 3 to 6 months after presentation. The one patient with an absent initial CTL response had prolonged symptoms, persistent viremia, and low CD4+ T-cell count. Neutralizing antibody activity was absent at the time of presentation in all five patients. These findings suggest that cellular immunity is involved in the initial control of virus replication in primary HIV-1 infection and indicate a role for CTL in protective immunity to HIV-1 in vivo.
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                Author and article information

                Journal
                J Exp Med
                The Journal of Experimental Medicine
                The Rockefeller University Press
                0022-1007
                1540-9538
                15 March 1999
                : 189
                : 6
                : 991-998
                Affiliations
                From [* ]The Aaron Diamond AIDS Research Center, The Rockefeller University, New York 10016; []Tulane Regional Primate Research Center, Covington, Louisiana 70433; the [§ ]Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30329; and []Los Alamos National Laboratory, Los Alamos, New Mexico 87545
                Author notes

                Address correspondence to David D. Ho, The Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Ave., New York, NY 10016. Phone: 212-448-5100; Fax: 212-725-1126; E-mail: dho@ 123456adarc.org

                Article
                10.1084/jem.189.6.991
                2193038
                10075982
                fd3657ac-fec7-47bb-9f8a-73c227695c7a
                Copyright @ 1999
                History
                : 22 December 1998
                : 19 January 1999
                Categories
                Articles

                Medicine
                simian immunodeficiency virus,macaque,okt8,viremia,cytotoxic  t lymphocyte
                Medicine
                simian immunodeficiency virus, macaque, okt8, viremia, cytotoxic  t lymphocyte

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