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Quantifying IFNgamma-secreting cells in exposed uninfected individuals.

Makedonas G, Merchant A, Pelley K, Tsoukas C, Bernard NF; Conference on Retroviruses and Opportunistic Infections.

7th Conf Retrovir Oppor Infect Jan 30 Feb 2 2000 Conf Retrovir Oppor Infect 7th 2000 San Franc Calif. 2000 Jan 30-Feb 2; 7: 189 (abstract no. 605).

McGill Univ. Hlth. Ctr., Canada.

Background: Some people remain HIV-seronegative despite exposure to the virus. Such individuals may have acquired protective immunity to HIV. We have tested a cohort of exposed uninfected (EU) subjects for the presence of HIV-specific IFNgamma secreting cells. A rationale exists for such activity like HIV-specific cytotoxic lymphocyte (CTL) activity playing a role in protection from seroconversion. Methods: Study subjects were typed for HLA alleles molecularly and/or serologically. Peripheral blood mononuclear cells were stimulated with a panel of synthetic HIV peptides that contain amino acid sequences with binding motifs for the HLA alleles expressed by each individual tested. The frequency of IFNgamma secreting cells was quantified using the ELISpot technique. A positive response was defined as any that produced a 2-fold increase over background in the number of IFNgamma secreting cells. Background responses were to no peptide and/or an irrelevant peptide. Phytohemagglutinin was the positive control stimulus. Results: Of the 15 EUs tested, 9 (60.0%) showed a positive response to a minimum of one peptide; 5 (33.3%) to multiple peptides; 2 (13.3%) to as many as six HLA-restricted peptides. In contrast, only 1 of 8 (12.5%) controls at low risk for HIV exposure yielded a positive reaction. The HLA-A2 immunodominant HIV peptides RT 476-484 and Gag 77-85 were recognized by 4 of ten (40.0%) and 2 of 10 (20%) HLA-A2+ subjects, respectively. Three of seven (42.9%) HLA-B35+ subjects responded to Gag p24-13. Conclusion: A significantly greater proportion of EUs than low risk controls had HIV-specific reactivity (9 of 15 EUs vs. 1 of 8 controls; p=0.03). The Elispot assay appears to have superior sensitivity than the HIV-specific CTL assay for detecting HIV-specific effector activity in EUs.

Publication Types:
  • Meeting Abstracts
Keywords:
  • AIDS Vaccines
  • Acquired Immunodeficiency Syndrome
  • Genes, gag
  • HIV
  • HIV Antibodies
  • HIV Antigens
  • HIV Core Protein p24
  • HIV Envelope Protein gp120
  • HIV Infections
  • HIV Long-Term Survivors
  • HIV Seronegativity
  • HIV Seropositivity
  • HLA Antigens
  • HLA-A2 Antigen
  • HLA-B35 Antigen
  • T-Lymphocytes, Cytotoxic
  • genetics
  • immunology
Other ID:
  • GWAIDS0005983
UI: 102243480

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