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*
Departments of Medical Microbiology, University of Nairobi, Nairobi, Kenya;
Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom;
Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada; and
§
Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Canada
Understanding how individuals with a high degree of HIV
exposure avoid persistent infection is paramount to HIV vaccine design.
Evidence suggests that mucosal immunity, particularly virus-specific
CTL, could be critically important in protection against sexually
acquired HIV infection. Therefore, we have looked for the presence of
HIV-specific CD8+ T cells in cervical mononuclear cells
from a subgroup of highly HIV-exposed but persistently seronegative
female sex workers in Nairobi. An enzyme-linked immunospot assay was
used to measure IFN-
release in response to known class I
HLA-restricted CTL epitope peptides using effector cells from the blood
and cervix of HIV-1-resistant and -infected sex workers and from
lower-risk uninfected controls. Eleven of 16 resistant sex workers had
HIV-specific CD8+ T cells in the cervix, and a similar
number had detectable responses in blood. Where both blood and cervical
responses were detected in the same individual, the specificity of the
responses was similar. Neither cervical nor blood responses were
detected in lower-risk control donors. HIV-specific CD8+ T
cell frequencies in the cervix of HIV-resistant sex workers were
slightly higher than in blood, while in HIV-infected donor cervical
response frequencies were markedly lower than blood, so that there was
relative enrichment of cervical responses in HIV-resistant compared
with HIV-infected donors. HIV-specific CD8+ T cell
responses in the absence of detectable HIV infection in the genital
mucosa of HIV-1-resistant sex workers may be playing an important part
in protective immunity against heterosexual HIV-1
transmission.
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S. Sabbaj, B. H. Edwards, M. K. Ghosh, K. Semrau, S. Cheelo, D. M. Thea, L. Kuhn, G. D. Ritter, M. J. Mulligan, P. A. Goepfert, et al. Human Immunodeficiency Virus-Specific CD8+ T Cells in Human Breast Milk J. Virol., June 27, 2002; 76(15): 7365 - 7373. [Abstract] [Full Text] [PDF]
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B. Peng, R. Voltan, L. Lim, Y. Edghill-Smith, S. Phogat, D. S. Dimitrov, K. Arora, M. Leno, S. Than, R. Woodward, et al. Rhesus Macaque Resistance to Mucosal Simian Immunodeficiency Virus Infection Is Associated with a Postentry Block in Viral Replication J. Virol., May 13, 2002; 76(12): 6016 - 6026. [Abstract] [Full Text] [PDF]
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B. H. Edwards, A. Bansal, S. Sabbaj, J. Bakari, M. J. Mulligan, and P. A. Goepfert Magnitude of Functional CD8+ T-Cell Responses to the Gag Protein of Human Immunodeficiency Virus Type 1 Correlates Inversely with Viral Load in Plasma J. Virol., March 1, 2002; 76(5): 2298 - 2305. [Abstract] [Full Text] [PDF]
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 M. W. Makgoba, N. Solomon, and T. J. P. Tucker Science, medicine, and the future: The search for an HIV vaccine BMJ, January 26, 2002; 324(7331): 211 - 213. [Full Text] [PDF]
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T. L.-Y. Chang, A. Mosoian, R. Pine, M. E. Klotman, and J. P. Moore A Soluble Factor(s) Secreted from CD8+ T Lymphocytes Inhibits Human Immunodeficiency Virus Type 1 Replication through STAT1 Activation J. Virol., January 15, 2002; 76(2): 569 - 581. [Abstract] [Full Text] [PDF]
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L. Stevceva, B. Kelsall, J. Nacsa, M. Moniuszko, Z. Hel, E. Tryniszewska, and G. Franchini Cervicovaginal Lamina Propria Lymphocytes: Phenotypic Characterization and Their Importance in Cytotoxic T-Lymphocyte Responses to Simian Immunodeficiency Virus SIVmac251 J. Virol., January 1, 2002; 76(1): 9 - 18. [Abstract] [Full Text] [PDF]
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Z. Ambrose, K. Larsen, J. Thompson, Y. Stevens, E. Finn, S.-L. Hu, and M. L. Bosch Evidence for Early Local Viral Replication and Local Production of Antiviral Immunity upon Mucosal Simian-Human Immunodeficiency Virus SHIV89.6 Infection in Macaca nemestrina J. Virol., September 15, 2001; 75(18): 8589 - 8596. [Abstract] [Full Text] [PDF]
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R. A. Kaslow, C. Rivers, J. Tang, T. J. Bender, P. A. Goepfert, R. El Habib, K. Weinhold, M. J. Mulligan, and the NIAID Aids Vaccine Evaluation Group Polymorphisms in HLA Class I Genes Associated with both Favorable Prognosis of Human Immunodeficiency Virus (HIV) Type 1 Infection and Positive Cytotoxic T-Lymphocyte Responses to ALVAC-HIV Recombinant Canarypox Vaccines J. Virol., September 15, 2001; 75(18): 8681 - 8689. [Abstract] [Full Text] [PDF]
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B. Korber, B. Gaschen, K. Yusim, R. Thakallapally, C. Kesmir, and V. Detours Evolutionary and immunological implications of contemporary HIV-1 variation Br. Med. Bull., September 1, 2001; 58(1): 19 - 42. [Abstract] [Full Text] [PDF]
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P. Hansasuta and S. L Rowland-Jones HIV-1 transmission and acute HIV-1 infection Br. Med. Bull., September 1, 2001; 58(1): 109 - 127. [Abstract] [Full Text] [PDF]
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T Hanke Prospect of a prophylactic vaccine for HIV Br. Med. Bull., September 1, 2001; 58(1): 205 - 218. [Abstract] [Full Text] [PDF]
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Y. Guan, J. B. Whitney, M. Detorio, and M. A. Wainberg Construction and In Vitro Properties of a Series of Attenuated Simian Immunodeficiency Viruses with All Accessory Genes Deleted J. Virol., May 1, 2001; 75(9): 4056 - 4067. [Abstract] [Full Text]
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W. S. Gallichan, R. N. Woolstencroft, T. Guarasci, M. J. McCluskie, H. L. Davis, and K. L. Rosenthal Intranasal Immunization with CpG Oligodeoxynucleotides as an Adjuvant Dramatically Increases IgA and Protection Against Herpes Simplex Virus-2 in the Genital Tract J. Immunol., March 1, 2001; 166(5): 3451 - 3457. [Abstract] [Full Text] [PDF]
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I. M. Belyakov, J. D. Ahlers, J. D. Clements, W. Strober, and J. A. Berzofsky Interplay of Cytokines and Adjuvants in the Regulation of Mucosal and Systemic HIV-Specific CTL J. Immunol., December 1, 2000; 165(11): 6454 - 6462. [Abstract] [Full Text] [PDF]
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C. Devito, K. Broliden, R. Kaul, L. Svensson, K. Johansen, P. Kiama, J. Kimani, L. Lopalco, S. Piconi, J. J. Bwayo, et al. Mucosal and Plasma IgA from HIV-1-Exposed Uninfected Individuals Inhibit HIV-1 Transcytosis Across Human Epithelial Cells J. Immunol., November 1, 2000; 165(9): 5170 - 5176. [Abstract] [Full Text] [PDF]
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P. S. Heeger, A. Valujskikh, and P. V. Lehmann23 Comprehensive Assessment of Determinant Specificity, Frequency, and Cytokine Signature of the Primed CD8 Cell Repertoire Induced by a Minor Transplantation Antigen J. Immunol., August 1, 2000; 165(3): 1278 - 1284. [Abstract] [Full Text] [PDF]
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