Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1993 Apr;78(4):611–615.

Cell-mediated immunity to HIV-1 in Walter Reed stages 1-6 individuals: correlation with virus burden.

R J Trauger 1, W K Giermakowska 1, F Ferre 1, P C Duffy 1, M R Wallace 1, D E Lewis 1, H J Beecham 1, K G Burnett 1, F C Jensen 1, D J Carlo 1
PMCID: PMC1421892  PMID: 8495981

Abstract

Cell-mediated immunity (CMI) to human immunodeficiency virus-1 (HIV-1) was assessed in a blinded fashion for a patient group (n = 79) representing Walter Reed (WR) stages 1-6. At the same time, viral load was quantitatively measured by two different methods, specifically, virus isolation and HIV viral DNA copy number as measured by the polymerase chain reaction (PCR). After unblinding it was determined that the ability to generate a lymphoproliferative response to an inactivated gp120-depleted HIV (HIV-ag) and tetanus toxoid diminished with advancing WR staging, with complete anergy to HIV-ag and tetanus at stage 6. As a group, individuals whose peripheral blood mononuclear cells (PBMC) proliferated to HIV-ag were either virus isolation negative or produced low levels of virus as measured by p24 antigen (< 250 pg p24) on day 7. Similarly, HIV DNA copy number in the HIV-ag responders was low (< 200 copies/4 x 10(5) PBMC). In contrast, antigen proliferation to tetanus toxoid did not correlate with virus load. Thus, clinical progression as defined by the WR staging system appears to coincide with a loss of CMI to HIV. More importantly, the low viral load measured in HIV-ag responders suggests a link between viral burden and CMI to HIV which might be exploited in the design of immunotherapies for HIV-infected individuals.

Full text

PDF
611

Selected References

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

  1. Ahearne P. M., Matthews T. J., Lyerly H. K., White G. C., Bolognesi D. P., Weinhold K. J. Cellular immune response to viral peptides in patients exposed to HIV. AIDS Res Hum Retroviruses. 1988 Aug;4(4):259–267. doi: 10.1089/aid.1988.4.259. [DOI] [PubMed] [Google Scholar]
  2. Ballet J. J., Couderc L. J., Rabian-Herzog C., Duval-Roy C., Janier M., Danon F., Clauvel J. P., Seligmann M. Impaired T-lymphocyte-dependent immune responses to microbial antigens in patients with HIV-1-associated persistent generalized lymphadenopathy. AIDS. 1988 Aug;2(4):291–297. doi: 10.1097/00002030-198808000-00009. [DOI] [PubMed] [Google Scholar]
  3. Clerici M., Stocks N. I., Zajac R. A., Boswell R. N., Bernstein D. C., Mann D. L., Shearer G. M., Berzofsky J. A. Interleukin-2 production used to detect antigenic peptide recognition by T-helper lymphocytes from asymptomatic HIV-seropositive individuals. Nature. 1989 Jun 1;339(6223):383–385. doi: 10.1038/339383a0. [DOI] [PubMed] [Google Scholar]
  4. Ferre F., Marchese A., Duffy P. C., Lewis D. E., Wallace M. R., Beecham H. J., Burnett K. G., Jensen F. C., Carlo D. J. Quantitation of HIV viral burden by PCR in HIV seropositive Navy personnel representing Walter Reed stages 1 to 6. AIDS Res Hum Retroviruses. 1992 Feb;8(2):269–275. doi: 10.1089/aid.1992.8.269. [DOI] [PubMed] [Google Scholar]
  5. Getchell J. P., Hicks D. R., Svinivasan A., Heath J. L., York D. A., Malonga M., Forthal D. N., Mann J. M., McCormick J. B. Human immunodeficiency virus isolated from a serum sample collected in 1976 in Central Africa. J Infect Dis. 1987 Nov;156(5):833–837. doi: 10.1093/infdis/156.5.833. [DOI] [PubMed] [Google Scholar]
  6. Giorgi J. V., Fahey J. L., Smith D. C., Hultin L. E., Cheng H. L., Mitsuyasu R. T., Detels R. Early effects of HIV on CD4 lymphocytes in vivo. J Immunol. 1987 Jun 1;138(11):3725–3730. [PubMed] [Google Scholar]
  7. Gottlieb M. S., Schroff R., Schanker H. M., Weisman J. D., Fan P. T., Wolf R. A., Saxon A. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med. 1981 Dec 10;305(24):1425–1431. doi: 10.1056/NEJM198112103052401. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Lane H. C., Fauci A. S. Immunologic abnormalities in the acquired immunodeficiency syndrome. Annu Rev Immunol. 1985;3:477–500. doi: 10.1146/annurev.iy.03.040185.002401. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Laurence J., Friedman S. M., Chartash E. K., Crow M. K., Posnett D. N. Human immunodeficiency virus infection of helper T cell clones. Early proliferative defects despite intact antigen-specific recognition and interleukin 4 secretion. J Clin Invest. 1989 Jun;83(6):1843–1848. doi: 10.1172/JCI114090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Melendez-Guerrero L. M., Nicholson J. K., McDougal J. S. Infection of human monocytes with HIV-1Ba-L. Effect on accessory cell function for T-cell proliferation in vitro. AIDS Res Hum Retroviruses. 1991 May;7(5):465–474. doi: 10.1089/aid.1991.7.465. [DOI] [PubMed] [Google Scholar]
  13. Michael N. L., Vahey M., Burke D. S., Redfield R. R. Viral DNA and mRNA expression correlate with the stage of human immunodeficiency virus (HIV) type 1 infection in humans: evidence for viral replication in all stages of HIV disease. J Virol. 1992 Jan;66(1):310–316. doi: 10.1128/jvi.66.1.310-316.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mullin G., Mayer L. Correlation of spontaneous suppressor cell activity with progression of human immunodeficiency virus infection. AIDS Res Hum Retroviruses. 1991 Apr;7(4):387–392. doi: 10.1089/aid.1991.7.387. [DOI] [PubMed] [Google Scholar]
  15. Powrie F., Mason D. Phenotypic and functional heterogeneity of CD4+ T cells. Immunol Today. 1988 Sep;9(9):274–277. doi: 10.1016/0167-5699(88)91309-6. [DOI] [PubMed] [Google Scholar]
  16. Reddy M. M., Grieco M. H. Cell-mediated immunity to recombinant human immunodeficiency virus (HIV) antigens in HIV-infected populations. J Infect Dis. 1989 Jan;159(1):120–122. doi: 10.1093/infdis/159.1.120. [DOI] [PubMed] [Google Scholar]
  17. Redfield R. R., Wright D. C., Tramont E. C. The Walter Reed staging classification for HTLV-III/LAV infection. N Engl J Med. 1986 Jan 9;314(2):131–132. doi: 10.1056/NEJM198601093140232. [DOI] [PubMed] [Google Scholar]
  18. Schnittman S. M., Greenhouse J. J., Psallidopoulos M. C., Baseler M., Salzman N. P., Fauci A. S., Lane H. C. Increasing viral burden in CD4+ T cells from patients with human immunodeficiency virus (HIV) infection reflects rapidly progressive immunosuppression and clinical disease. Ann Intern Med. 1990 Sep 15;113(6):438–443. doi: 10.7326/0003-4819-113-6-438. [DOI] [PubMed] [Google Scholar]
  19. Schnittman S. M., Lane H. C., Greenhouse J., Justement J. S., Baseler M., Fauci A. S. Preferential infection of CD4+ memory T cells by human immunodeficiency virus type 1: evidence for a role in the selective T-cell functional defects observed in infected individuals. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6058–6062. doi: 10.1073/pnas.87.16.6058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Swain S. L., Weinberg A. D., English M. CD4+ T cell subsets. Lymphokine secretion of memory cells and of effector cells that develop from precursors in vitro. J Immunol. 1990 Mar 1;144(5):1788–1799. [PubMed] [Google Scholar]
  21. Viscidi R. P., Mayur K., Lederman H. M., Frankel A. D. Inhibition of antigen-induced lymphocyte proliferation by Tat protein from HIV-1. Science. 1989 Dec 22;246(4937):1606–1608. doi: 10.1126/science.2556795. [DOI] [PubMed] [Google Scholar]
  22. Wahren B., Morfeldt-Månsson L., Biberfeld G., Moberg L., Ljungman P., Nordlund S., Bredberg-Rådén U., Werner A., Löwer J., Kurth R. Impaired specific cellular response to HTLV-III before other immune defects in patients with HTLV-III infection. N Engl J Med. 1986 Aug 7;315(6):393–394. [PubMed] [Google Scholar]
  23. Wahren B., Morfeldt-Månsson L., Biberfeld G., Moberg L., Sönnerborg A., Ljungman P., Werner A., Kurth R., Gallo R., Bolognesi D. Characteristics of the specific cell-mediated immune response in human immunodeficiency virus infection. J Virol. 1987 Jun;61(6):2017–2023. doi: 10.1128/jvi.61.6.2017-2023.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES