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. 1995 Oct;102(1):26–30. doi: 10.1111/j.1365-2249.1995.tb06631.x

In vitro anti-HIV-1 antibody production in subjects in different stages of HIV-1 infection.

S Rusconi 1, A Riva 1, L Meroni 1, G Zehender 1, F Cocchi 1, L Scapellato 1, M Galli 1
PMCID: PMC1553321  PMID: 7554395

Abstract

We evaluated the in vitro antibody production from peripheral blood mononuclear cells (PBMC) against HIV-1 proteins in infected adults. Fifty-four HIV-1 infected patients (four recent seroconverters, 15 asymptomatics with a CD4 count higher than 500/microliters, 27 asymptomatics with a CD4 count between 200 and 500/microliters and eight symptomatic patients) were tested. PBMC were incubated in the presence or absence of 1% pokeweed mitogen (PWM) at 37 degrees C for 8 days. Western blot assay, p24 antigen ELISA and anti-p24 antibody ELISA were performed on serum and culture supernatants. Spontaneous production of anti-env antibody in culture supernatants was evidenced in all subjects. All the positive supernatants for anti-core antibodies (18/54) were derived from asymptomatic patients. PBMC from recent seroconverters and from symptomatic patients did not produce any anti-core antibody. Antibody production decreased after stimulation with PWM. The concentration of p24 antigen did not significantly increase in p24 positive supernatants following acidification (P = 0.1), suggesting that the inability to detect p24 antibody was not due to the anti-p24 antibody complexed to p24 antigen in culture supernatants. In vitro production of anti-p24 antibodies was significantly more frequent in asymptomatic subjects with high CD4+ cell counts (P = 0.02) and was absent in recent seroconverters. This last finding suggests that during the initial phases of the infection, anti-p24 antibody production may be restricted to cells residing in lymphoid organs. In addition, the lower percentage of anti-core antibody in people with low CD4+ cell counts is not merely a consequence of the binding of the antibody to an increased amount of antigen, but probably reflects an impaired production or a sequestration of producing cells in lymphoid tissue during the late stages of the infection.

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Selected References

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  1. Albert J., Gaines H., Sönnerborg A., Nyström G., Pehrson P. O., Chiodi F., von Sydow M., Moberg L., Lidman K., Christensson B. Isolation of human immunodeficiency virus (HIV) from plasma during primary HIV infection. J Med Virol. 1987 Sep;23(1):67–73. doi: 10.1002/jmv.1890230108. [DOI] [PubMed] [Google Scholar]
  2. Allain J. P., Laurian Y., Einstein M. H., Braun B. P., Delaney S. R., Stephens J. E., Daluga C. K., Dahlen S. J., Knigge K. M. Monitoring of specific antibodies to human immunodeficiency virus structural proteins: clinical significance. Blood. 1991 Mar 1;77(5):1118–1123. [PubMed] [Google Scholar]
  3. Amadori A., De Rossi A., Faulkner-Valle G. P., Chieco-Bianchi L. Spontaneous in vitro production of virus-specific antibody by lymphocytes from HIV-infected subjects. Clin Immunol Immunopathol. 1988 Mar;46(3):342–351. doi: 10.1016/0090-1229(88)90053-0. [DOI] [PubMed] [Google Scholar]
  4. Amadori A., Zamarchi R., Veronese M. L., Panozzo M., Mazza M. R., Barelli A., Borri A., Chieco-Bianchi L. B-cell activation during HIV-1 infection. III. Down-regulating effect of mitogens. AIDS. 1991 Jul;5(7):821–828. doi: 10.1097/00002030-199107000-00005. [DOI] [PubMed] [Google Scholar]
  5. Aucouturier P., Couderc L. J., Gouet D., Danon F., Gombert J., Matheron S., Saimot A. G., Clauvel J. P., Preud'homme J. L. Serum immunoglobulin G subclass dysbalances in the lymphadenopathy syndrome and acquired immune deficiency syndrome. Clin Exp Immunol. 1986 Jan;63(1):234–240. [PMC free article] [PubMed] [Google Scholar]
  6. Burkes R. L., Abo W., Levine A. M., Linker-Israeli M., Parker J. W., Gill P. S., Krailo M., Horwitz D. A. Characterization of immunologic function in homosexual men with persistent, generalized lymphadenopathy and acquired immune deficiency syndrome. Cancer. 1987 Feb 15;59(4):731–738. doi: 10.1002/1097-0142(19870215)59:4<731::aid-cncr2820590412>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  7. Chargelegue D., Stanley C. M., O'Toole C. M., Colvin B. T., Steward M. W. The affinity of IgG antibodies to gag p24 and p17 in HIV-1-infected patients correlates with disease progression. Clin Exp Immunol. 1995 Feb;99(2):175–181. doi: 10.1111/j.1365-2249.1995.tb05529.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cheingsong-Popov R., Panagiotidi C., Bowcock S., Aronstam A., Wadsworth J., Weber J. Relation between humoral responses to HIV gag and env proteins at seroconversion and clinical outcome of HIV infection. BMJ. 1991 Jan 5;302(6767):23–26. doi: 10.1136/bmj.302.6767.23. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Delfraissy J. F., Wallon C., Boué F., Goujard C., Barré-Sinoussi F., Galanaud P. HIV-induced, HIV-specific in vitro antibody response by B-cells from HIV-seropositive individuals. AIDS. 1992 Jan;6(1):55–63. doi: 10.1097/00002030-199201000-00007. [DOI] [PubMed] [Google Scholar]
  10. Edelman A. S., Zolla-Pazner S. Response of mononuclear cells from HIV-infected patients to B-cell mitogens: correlation with immunological and clinical features of disease progression. AIDS. 1990 Sep;4(9):859–864. doi: 10.1097/00002030-199009000-00004. [DOI] [PubMed] [Google Scholar]
  11. Farzadegan H., Chmiel J. S., Odaka N., Ward L., Poggensee L., Saah A., Phair J. P. Association of antibody to human immunodeficiency virus type 1 core protein (p24), CD4+ lymphocyte number, and AIDS-free time. J Infect Dis. 1992 Dec;166(6):1217–1222. doi: 10.1093/infdis/166.6.1217. [DOI] [PubMed] [Google Scholar]
  12. Fenouillet E., Blanes N., Coutellier A., Demarquest J., Rozenbaum W., Gluckman J. C. Monitoring of antibodies against human immunodeficiency virus type 1 p25 core protein as prognostic marker. J Infect Dis. 1992 Sep;166(3):611–616. doi: 10.1093/infdis/166.3.611. [DOI] [PubMed] [Google Scholar]
  13. Fishbein D. B., Kaplan J. E., Spira T. J., Miller B., Schonberger L. B., Pinsky P. F., Getchell J. P., Kalyanaraman V. S., Braude J. S. Unexplained lymphadenopathy in homosexual men. A longitudinal study. JAMA. 1985 Aug 16;254(7):930–935. [PubMed] [Google Scholar]
  14. Gaines H., von Sydow M. A., von Stedingk L. V., Biberfeld G., Böttiger B., Hansson L. O., Lundbergh P., Sönnerborg A. B., Wasserman J., Strannegåard O. O. Immunological changes in primary HIV-1 infection. AIDS. 1990 Oct;4(10):995–999. doi: 10.1097/00002030-199010000-00008. [DOI] [PubMed] [Google Scholar]
  15. Habeshaw J. A., Dalgleish A. G., Bountiff L., Newell A. L., Wilks D., Walker L. C., Manca F. AIDS pathogenesis: HIV envelope and its interaction with cell proteins. Immunol Today. 1990 Nov;11(11):418–425. doi: 10.1016/0167-5699(90)90162-3. [DOI] [PubMed] [Google Scholar]
  16. Ho D. D., Pomerantz R. J., Kaplan J. C. Pathogenesis of infection with human immunodeficiency virus. N Engl J Med. 1987 Jul 30;317(5):278–286. doi: 10.1056/NEJM198707303170505. [DOI] [PubMed] [Google Scholar]
  17. Hofmann B., Lindhardt B. O., Gerstoft J., Petersen C. S., Platz P., Ryder L. P., Odum N., Dickmeiss E., Nielsen P. B., Ullman S. Lymphocyte transformation response to pokeweed mitogen as a predictive marker for development of AIDS and AIDS related symptoms in homosexual men with HIV antibodies. Br Med J (Clin Res Ed) 1987 Aug 1;295(6593):293–296. doi: 10.1136/bmj.295.6593.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jurriaans S., Dekker J. T., de Ronde A. HIV-1 viral DNA load in peripheral blood mononuclear cells from seroconverters and long-term infected individuals. AIDS. 1992 Jul;6(7):635–641. doi: 10.1097/00002030-199207000-00004. [DOI] [PubMed] [Google Scholar]
  19. Keet I. P., Krijnen P., Koot M., Lange J. M., Miedema F., Goudsmit J., Coutinho R. A. Predictors of rapid progression to AIDS in HIV-1 seroconverters. AIDS. 1993 Jan;7(1):51–57. doi: 10.1097/00002030-199301000-00008. [DOI] [PubMed] [Google Scholar]
  20. Krowka J. F., Stites D. P., Jain S., Steimer K. S., George-Nascimento C., Gyenes A., Barr P. J., Hollander H., Moss A. R., Homsy J. M. Lymphocyte proliferative responses to human immunodeficiency virus antigens in vitro. J Clin Invest. 1989 Apr;83(4):1198–1203. doi: 10.1172/JCI114001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lane H. C., Masur H., Edgar L. C., Whalen G., Rook A. H., Fauci A. S. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1983 Aug 25;309(8):453–458. doi: 10.1056/NEJM198308253090803. [DOI] [PubMed] [Google Scholar]
  22. Lange J. M., Paul D. A., Huisman H. G., de Wolf F., van den Berg H., Coutinho R. A., Danner S. A., van der Noordaa J., Goudsmit J. Persistent HIV antigenaemia and decline of HIV core antibodies associated with transition to AIDS. Br Med J (Clin Res Ed) 1986 Dec 6;293(6560):1459–1462. doi: 10.1136/bmj.293.6560.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Miedema F., Petit A. J., Terpstra F. G., Schattenkerk J. K., de Wolf F., Al B. J., Roos M., Lange J. M., Danner S. A., Goudsmit J. Immunological abnormalities in human immunodeficiency virus (HIV)-infected asymptomatic homosexual men. HIV affects the immune system before CD4+ T helper cell depletion occurs. J Clin Invest. 1988 Dec;82(6):1908–1914. doi: 10.1172/JCI113809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Moss A. R., Bacchetti P., Osmond D., Krampf W., Chaisson R. E., Stites D., Wilber J., Allain J. P., Carlson J. Seropositivity for HIV and the development of AIDS or AIDS related condition: three year follow up of the San Francisco General Hospital cohort. Br Med J (Clin Res Ed) 1988 Mar 12;296(6624):745–750. doi: 10.1136/bmj.296.6624.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nishanian P., Huskins K. R., Stehn S., Detels R., Fahey J. L. A simple method for improved assay demonstrates that HIV p24 antigen is present as immune complexes in most sera from HIV-infected individuals. J Infect Dis. 1990 Jul;162(1):21–28. doi: 10.1093/infdis/162.1.21. [DOI] [PubMed] [Google Scholar]
  26. Pedersen C., Dickmeiss E., Gaub J., Ryder L. P., Platz P., Lindhardt B. O., Lundgren J. D. T-cell subset alterations and lymphocyte responsiveness to mitogens and antigen during severe primary infection with HIV: a case series of seven consecutive HIV seroconverters. AIDS. 1990 Jun;4(6):523–526. doi: 10.1097/00002030-199006000-00005. [DOI] [PubMed] [Google Scholar]
  27. Polk B. F., Fox R., Brookmeyer R., Kanchanaraksa S., Kaslow R., Visscher B., Rinaldo C., Phair J. Predictors of the acquired immunodeficiency syndrome developing in a cohort of seropositive homosexual men. N Engl J Med. 1987 Jan 8;316(2):61–66. doi: 10.1056/NEJM198701083160201. [DOI] [PubMed] [Google Scholar]
  28. Schnittman S. M., Lane H. C., Higgins S. E., Folks T., Fauci A. S. Direct polyclonal activation of human B lymphocytes by the acquired immune deficiency syndrome virus. Science. 1986 Sep 5;233(4768):1084–1086. doi: 10.1126/science.3016902. [DOI] [PubMed] [Google Scholar]
  29. Shirai A., Cosentino M., Leitman-Klinman S. F., Klinman D. M. Human immunodeficiency virus infection induces both polyclonal and virus-specific B cell activation. J Clin Invest. 1992 Feb;89(2):561–566. doi: 10.1172/JCI115621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Stahl R. E., Friedman-Kien A., Dubin R., Marmor M., Zolla-Pazner S. Immunologic abnormalities in homosexual men. Relationship to Kaposi's sarcoma. Am J Med. 1982 Aug;73(2):171–178. doi: 10.1016/0002-9343(82)90174-7. [DOI] [PubMed] [Google Scholar]
  31. Teeuwsen V. J., Lange J. M., Keet R., Schattenkerk J. K., Debouck C., van den Akker R., Goudsmit J., Osterhaus A. D. Low number of functionally active B lymphocytes in the peripheral blood of HIV-1-seropositive individuals with low p24-specific serum antibody titers. AIDS. 1991 Aug;5(8):971–979. doi: 10.1097/00002030-199108000-00008. [DOI] [PubMed] [Google Scholar]
  32. Teeuwsen V. J., Logtenberg T., Siebelink K. H., Lange J. M., Goudsmit J., Uytdehaag F. G., Osterhaus A. D. Analysis of the antigen- and mitogen-induced differentiation of B lymphocytes from asymptomatic human immunodeficiency virus-seropositive male homosexuals. Discrepancy between T cell-dependent and T cell-independent activation. J Immunol. 1987 Nov 1;139(9):2929–2935. [PubMed] [Google Scholar]
  33. Terpstra F. G., Al B. J., Roos M. T., De Wolf F., Goudsmit J., Schellekens P. T., Miedema F. Longitudinal study of leukocyte functions in homosexual men seroconverted for HIV: rapid and persistent loss of B cell function after HIV infection. Eur J Immunol. 1989 Apr;19(4):667–673. doi: 10.1002/eji.1830190415. [DOI] [PubMed] [Google Scholar]
  34. Vendrell J. P., Segondy M., Ducos J., Reynes J., Huguet M. F., Nicolas J. C., Serre A. Analysis of the spontaneous in vitro anti-HIV-1 antibody secretion by peripheral blood mononuclear cells in HIV-1 infection. Clin Exp Immunol. 1991 Feb;83(2):197–202. doi: 10.1111/j.1365-2249.1991.tb05614.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yarchoan R., Redfield R. R., Broder S. Mechanisms of B cell activation in patients with acquired immunodeficiency syndrome and related disorders. Contribution of antibody-producing B cells, of Epstein-Barr virus-infected B cells, and of immunoglobulin production induced by human T cell lymphotropic virus, type III/lymphadenopathy-associated virus. J Clin Invest. 1986 Aug;78(2):439–447. doi: 10.1172/JCI112595. [DOI] [PMC free article] [PubMed] [Google Scholar]

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