Role of CD8+ cell-produced anti-viral factors in protective immunity in HIV-2-exposed but seronegative macaques resistant to intrarectal SIVsm challenge.
The cell-mediated immune response is likely to be important in controlling HIV/SIV infection. There is evidence that beta-chemokines and other, as yet unknown, anti-viral factors play a role in host defence against HIV infection. We reported previously that HIV-2 exposed but seronegative cynomolgus macaques developed SIV-specific cytotoxic T lymphocytes and were resistant to mucosal SIV challenge. The aim of this study was to examine CD8+ cell-dependent production of beta-chemokines and other anti-viral factors in these macaques. The animals, selected from among 17 monkeys enrolled in two separate experiments, were either treated with an anti-viral drug or immunized passively with HIV-2 antibody-positive serum. Three of these monkeys were protected against repeated HIV-2 challenge and were also able to control SIV infection 3 years later. Control samples were obtained from four macaques that became SIV infected and from 39 naïve animals. The three resistant monkeys showed significantly higher production of RANTES and MIP-1alpha than the 39 naïve animals. In addition, SIV infection was suppressed by CD8+ cell culture supernatants of these monkeys. However, antibodies to chemokines only partially neutralized CD8+ cell-mediated SIV suppression indicating that the anti-viral activity observed in these monkeys was the result of combined action of several inhibitory factors.
Swedish Institute for Infectious Disease Control and Microbiology and Tumorbiology Center, Karolinska Institute, SE-171 82 Solna, Sweden. raja.ahmed@smi.ki.se
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Ahmed
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Nilsson
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Biberfeld
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Thorstensson
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis; D019742:Chemokines, CC / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D005260:Female; D018023:HIV Seronegativity / Q000276:immunology; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D007116:Immunization, Passive; D007700:Kinetics; D008252:Macaca fascicularis; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D008297:Male; D012007:Rectum / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D014779:Virus Replication
D000998:Antiviral Agents; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins