Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Mar;93(3):1293–1297. doi: 10.1172/JCI117085

Human immunodeficiency virus (HIV) nef-specific cytotoxic T lymphocytes in noninfected heterosexual contact of HIV-infected patients.

P Langlade-Demoyen 1, N Ngo-Giang-Huong 1, F Ferchal 1, E Oksenhendler 1
PMCID: PMC294083  PMID: 8132769

Abstract

We report on the detection of HIV-specific cytotoxic T lymphocytes (CTL) among 23 regular partners of HIV-infected individuals. 15 of the 46 individuals enrolled in the study were positive for HLA-A2.1 typing. Among the 23 contacts studied, 7 were seropositive and 16 were seronegative on repeated tests. None of the 16 seronegative contacts were positive for p24 antigenemia nor were they positive by the lymphocytes coculture assay, although, in two instances HIV-1 DNA could be detected by PCR (in one case using a gag SK 38/39 primer, and in the other using a primer for the pol P3/P4 primer). These two individuals remained seronegative for 18 and 36 mo, respectively. HIV-specific cytotoxicity was performed in the 15 HLA-A2.1 subjects (7 indexes, 2 seropositive contacts, and 6 seronegative contacts) and in 4 HLA-matched HIV negative donors. CTL specific for env, gag, or nef proteins could not be detected in unstimulated bulk cultures of peripheral blood lymphocytes in any of the six seronegative contacts. However, using a limiting dilution assay we found an usually high frequency of HIV nef-specific CTL precursors (CTLp) for HIV env and gag was very similar to that observed in seronegative HLA-matched healthy donors. Because no presence of HIV could be demonstrated in these individuals, these findings argue against the possibility of a silent HIV infection and suggest that a CTL response against nef may be involved in a rapid and effective clearance of the virus after sexual exposure.

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albert J., Pehrson P. O., Schulman S., Håkansson C., Lövhagen G. B., Berglund O., Beckman S., Fenyö E. M. HIV isolation and antigen detection in infected individuals and their seronegative sexual partners. AIDS. 1988 Apr;2(2):107–111. doi: 10.1097/00002030-198804000-00006. [DOI] [PubMed] [Google Scholar]
  2. Baltimore D., Feinberg M. B. HIV revealed: toward a natural history of the infection. N Engl J Med. 1989 Dec 14;321(24):1673–1675. doi: 10.1056/NEJM198912143212409. [DOI] [PubMed] [Google Scholar]
  3. Brettler D. B., Somasundaran M., Forsberg A. F., Krause E., Sullivan J. L. Silent human immunodeficiency virus type 1 infection: a rare occurrence in a high-risk heterosexual population. Blood. 1992 Nov 1;80(9):2396–2400. [PubMed] [Google Scholar]
  4. Chenciner N., Michel F., Dadaglio G., Langlade-Demoyen P., Hoffenbach A., Leroux A., Garcia-Pons F., Rautmann G., Guy B., Guillon J. M. Multiple subsets of HIV-specific cytotoxic T lymphocytes in humans and in mice. Eur J Immunol. 1989 Sep;19(9):1537–1544. doi: 10.1002/eji.1830190904. [DOI] [PubMed] [Google Scholar]
  5. Cheynier R., Langlade-Demoyen P., Marescot M. R., Blanche S., Blondin G., Wain-Hobson S., Griscelli C., Vilmer E., Plata F. Cytotoxic T lymphocyte responses in the peripheral blood of children born to human immunodeficiency virus-1-infected mothers. Eur J Immunol. 1992 Sep;22(9):2211–2217. doi: 10.1002/eji.1830220905. [DOI] [PubMed] [Google Scholar]
  6. Clerici M., Giorgi J. V., Chou C. C., Gudeman V. K., Zack J. A., Gupta P., Ho H. N., Nishanian P. G., Berzofsky J. A., Shearer G. M. Cell-mediated immune response to human immunodeficiency virus (HIV) type 1 in seronegative homosexual men with recent sexual exposure to HIV-1. J Infect Dis. 1992 Jun;165(6):1012–1019. doi: 10.1093/infdis/165.6.1012. [DOI] [PubMed] [Google Scholar]
  7. Delassus S., Cheynier R., Wain-Hobson S. Evolution of human immunodeficiency virus type 1 nef and long terminal repeat sequences over 4 years in vivo and in vitro. J Virol. 1991 Jan;65(1):225–231. doi: 10.1128/jvi.65.1.225-231.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ensoli F., Fiorelli V., Mezzaroma I., D'Offizi G., Rainaldi L., Luzi G., Fiorilli M., Aiuti F. Plasma viraemia in seronegative HIV-1-infected individuals. AIDS. 1991 Oct;5(10):1195–1199. doi: 10.1097/00002030-199110000-00007. [DOI] [PubMed] [Google Scholar]
  9. Farzadegan H., Imagawa D., Gupta P., Lee M. H., Jacobson L., Saah A., Grovit K., Rinaldo C. R., Jr, Polk B. F. The effect of fresh lymphocytes on increased sensitivity of HIV-1 isolation: a multicenter study. J Acquir Immune Defic Syndr. 1990;3(10):981–986. [PubMed] [Google Scholar]
  10. Groopman J. E., Caiazzo T., Thomas M. A., Ferriani R. A., Saltzman S., Moon M., Seage G., Horsburgh C. R., Jr, Mayer K. Lack of evidence of prolonged human immunodeficiency virus infection before antibody seroconversion. Blood. 1988 Jun;71(6):1752–1754. [PubMed] [Google Scholar]
  11. Hewlett I. K., Laurian Y., Epstein J., Hawthorne C. A., Ruta M., Allain J. P. Assessment by gene amplification and serological markers of transmission of HIV-1 from hemophiliacs to their sexual partners and secondarily to their children. J Acquir Immune Defic Syndr. 1990;3(7):714–720. [PubMed] [Google Scholar]
  12. Hoffenbach A., Langlade-Demoyen P., Dadaglio G., Vilmer E., Michel F., Mayaud C., Autran B., Plata F. Unusually high frequencies of HIV-specific cytotoxic T lymphocytes in humans. J Immunol. 1989 Jan 15;142(2):452–462. [PubMed] [Google Scholar]
  13. Hoffmann G. W., Kion T. A., Grant M. D. An idiotypic network model of AIDS immunopathogenesis. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3060–3064. doi: 10.1073/pnas.88.8.3060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Horsburgh C. R., Jr, Ou C. Y., Jason J., Holmberg S. D., Lifson A. R., Moore J. L., Ward J. W., Seage G. R., Mayer K. H., Evatt B. L. Concordance of polymerase chain reaction with human immunodeficiency virus antibody detection. J Infect Dis. 1990 Aug;162(2):542–545. doi: 10.1093/infdis/162.2.542. [DOI] [PubMed] [Google Scholar]
  15. Horsburgh C. R., Jr, Ou C. Y., Jason J., Holmberg S. D., Longini I. M., Jr, Schable C., Mayer K. H., Lifson A. R., Schochetman G., Ward J. W. Duration of human immunodeficiency virus infection before detection of antibody. Lancet. 1989 Sep 16;2(8664):637–640. doi: 10.1016/s0140-6736(89)90892-1. [DOI] [PubMed] [Google Scholar]
  16. Imagawa D. T., Lee M. H., Wolinsky S. M., Sano K., Morales F., Kwok S., Sninsky J. J., Nishanian P. G., Giorgi J., Fahey J. L. Human immunodeficiency virus type 1 infection in homosexual men who remain seronegative for prolonged periods. N Engl J Med. 1989 Jun 1;320(22):1458–1462. doi: 10.1056/NEJM198906013202205. [DOI] [PubMed] [Google Scholar]
  17. Imagawa D., Detels R. HIV-1 in seronegative homosexual men. N Engl J Med. 1991 Oct 24;325(17):1250–1251. doi: 10.1056/NEJM199110243251713. [DOI] [PubMed] [Google Scholar]
  18. Jackson J. B., Kwok S. Y., Hopsicker J. S., Sannerud K. J., Sninsky J. J., Edson J. R., Balfour H. H., Jr Absence of HIV-1 infection in antibody-negative sexual partners of HIV-1 infected hemophiliacs. Transfusion. 1989 Mar-Apr;29(3):265–267. doi: 10.1046/j.1537-2995.1989.29389162735.x. [DOI] [PubMed] [Google Scholar]
  19. Langlade-Demoyen P., Michel F., Hoffenbach A., Vilmer E., Dadaglio G., Garicia-Pons F., Mayaud C., Autran B., Wain-Hobson S., Plata F. Immune recognition of AIDS virus antigens by human and murine cytotoxic T lymphocytes. J Immunol. 1988 Sep 15;141(6):1949–1957. [PubMed] [Google Scholar]
  20. Laure F., Courgnaud V., Rouzioux C., Blanche S., Veber F., Burgard M., Jacomet C., Griscelli C., Brechot C. Detection of HIV1 DNA in infants and children by means of the polymerase chain reaction. Lancet. 1988 Sep 3;2(8610):538–541. doi: 10.1016/s0140-6736(88)92659-1. [DOI] [PubMed] [Google Scholar]
  21. Lefrere J. J., Mariotti M., Courouce A. M., Rouger P., Salmon C., Vittecoq D. Polymerase chain reaction testing of HIV-1 seronegative at-risk individuals. Lancet. 1990 Jun 9;335(8702):1400–1401. doi: 10.1016/0140-6736(90)91277-h. [DOI] [PubMed] [Google Scholar]
  22. Loche M., Mach B. Identification of HIV-infected seronegative individuals by a direct diagnostic test based on hybridisation to amplified viral DNA. Lancet. 1988 Aug 20;2(8608):418–421. doi: 10.1016/s0140-6736(88)90412-6. [DOI] [PubMed] [Google Scholar]
  23. Mariotti M., Lefrère J. J., Noel B., Ferrer-Le-Coeur F., Vittecoq D., Girot R., Bosser C., Couroucé A. M., Salmon C., Rouger P. DNA amplification of HIV-1 in seropositive individuals and in seronegative at-risk individuals. AIDS. 1990 Jul;4(7):633–637. doi: 10.1097/00002030-199007000-00004. [DOI] [PubMed] [Google Scholar]
  24. Meyerhans A., Dadaglio G., Vartanian J. P., Langlade-Demoyen P., Frank R., Asjö B., Plata F., Wain-Hobson S. In vivo persistence of a HIV-1-encoded HLA-B27-restricted cytotoxic T lymphocyte epitope despite specific in vitro reactivity. Eur J Immunol. 1991 Oct;21(10):2637–2640. doi: 10.1002/eji.1830211051. [DOI] [PubMed] [Google Scholar]
  25. Nielsen C., Teglbjaerg L. S., Pedersen C., Lundgren J. D., Nielsen C. M., Vestergaard B. F. Prevalence of HIV infection in seronegative high-risk individuals examined by virus isolation and PCR. J Acquir Immune Defic Syndr. 1991;4(11):1107–1111. [PubMed] [Google Scholar]
  26. Ou C. Y., Kwok S., Mitchell S. W., Mack D. H., Sninsky J. J., Krebs J. W., Feorino P., Warfield D., Schochetman G. DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. Science. 1988 Jan 15;239(4837):295–297. doi: 10.1126/science.3336784. [DOI] [PubMed] [Google Scholar]
  27. Phillips R. E., Rowland-Jones S., Nixon D. F., Gotch F. M., Edwards J. P., Ogunlesi A. O., Elvin J. G., Rothbard J. A., Bangham C. R., Rizza C. R. Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature. 1991 Dec 12;354(6353):453–459. doi: 10.1038/354453a0. [DOI] [PubMed] [Google Scholar]
  28. Plata F., Autran B., Martins L. P., Wain-Hobson S., Raphaël M., Mayaud C., Denis M., Guillon J. M., Debré P. AIDS virus-specific cytotoxic T lymphocytes in lung disorders. Nature. 1987 Jul 23;328(6128):348–351. doi: 10.1038/328348a0. [DOI] [PubMed] [Google Scholar]
  29. Ranki A., Valle S. L., Krohn M., Antonen J., Allain J. P., Leuther M., Franchini G., Krohn K. Long latency precedes overt seroconversion in sexually transmitted human-immunodeficiency-virus infection. Lancet. 1987 Sep 12;2(8559):589–593. doi: 10.1016/s0140-6736(87)92985-0. [DOI] [PubMed] [Google Scholar]
  30. Rowland-Jones S. L., Nixon D. F., Aldhous M. C., Gotch F., Ariyoshi K., Hallam N., Kroll J. S., Froebel K., McMichael A. HIV-specific cytotoxic T-cell activity in an HIV-exposed but uninfected infant. Lancet. 1993 Apr 3;341(8849):860–861. doi: 10.1016/0140-6736(93)93063-7. [DOI] [PubMed] [Google Scholar]
  31. Saiki R. K., Scharf S., Faloona F., Mullis K. B., Horn G. T., Erlich H. A., Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. doi: 10.1126/science.2999980. [DOI] [PubMed] [Google Scholar]
  32. Soriano V., Hewlett I., Tor J., Clotet B., Epstein J., Foz M. Silent HIV infection in heterosexual partners of seropositive drug abusers in Spain. Lancet. 1990 Apr 7;335(8693):860–860. doi: 10.1016/0140-6736(90)90978-e. [DOI] [PubMed] [Google Scholar]
  33. Taswell C. Limiting dilution assays for the determination of immunocompetent cell frequencies. I. Data analysis. J Immunol. 1981 Apr;126(4):1614–1619. [PubMed] [Google Scholar]
  34. Wolinsky S. M., Rinaldo C. R., Kwok S., Sninsky J. J., Gupta P., Imagawa D., Farzadegan H., Jacobson L. P., Grovit K. S., Lee M. H. Human immunodeficiency virus type 1 (HIV-1) infection a median of 18 months before a diagnostic western blot. Evidence from a cohort of homosexual men. Ann Intern Med. 1989 Dec 15;111(12):961–972. doi: 10.7326/0003-4819-111-12-961. [DOI] [PubMed] [Google Scholar]
  35. Young J. A. HIV and HLA similarity. Nature. 1988 May 19;333(6170):215–215. doi: 10.1038/333215c0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES