• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Apr 30, 1996; 93(9): 4386–4391.
PMCID: PMC39547

Kinetics of cytokine expression during primary human immunodeficiency virus type 1 infection.

Abstract

In the present study, we have determined the kinetics of constitutive expression of a panel of cytokines [interleukin (IL) 2, IL-4, IL-6, IL-10, interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha)] in sequential peripheral blood mononuclear cell samples from nine individuals with primary human immunodeficiency virus infection. Expression of IL-2 and IL-4 was barely detected in peripheral blood mononuclear cells. However, substantial levels of IL-2 expression were found in mononuclear cells isolated from lymph node. Expression of IL-6 was detected in only three of nine patients, and IL-6 expression was observed when transition from the acute to the chronic phase had already occurred. Expression of IL-10 and TNF-alpha was consistently observed in all patients tested, and levels of both cytokines were either stable or progressively increased over time. Similar to IL-10 and TNF-alpha, IFN-gamma expression was detected in all patients; however, in five of nine patients, IFN-gamma expression peaked very early during primary infection. The early peak in IFN-gamma expression coincided with oligoclonal expansions of CD8+ T cells in five of six patients, and CD8+ T cells mostly accounted for the expression of this cytokine. These results indicate that high levels of expression of proinflammatory cytokines are associated with primary infection and that the cytokine response during this phase of infection is strongly influenced by oligoclonal expansions of CD8+ T cells.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Tindall B, Cooper DA. Primary HIV infection: host responses and intervention strategies. AIDS. 1991 Jan;5(1):1–14. [PubMed]
  • Pantaleo G, Graziosi C, Fauci AS. New concepts in the immunopathogenesis of human immunodeficiency virus infection. N Engl J Med. 1993 Feb 4;328(5):327–335. [PubMed]
  • Daar ES, Moudgil T, Meyer RD, Ho DD. Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. N Engl J Med. 1991 Apr 4;324(14):961–964. [PubMed]
  • Clark SJ, Saag MS, Decker WD, Campbell-Hill S, Roberson JL, Veldkamp PJ, Kappes JC, Hahn BH, Shaw GM. High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection. N Engl J Med. 1991 Apr 4;324(14):954–960. [PubMed]
  • Koup RA, Safrit JT, Cao Y, Andrews CA, McLeod G, Borkowsky W, Farthing C, Ho DD. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol. 1994 Jul;68(7):4650–4655. [PMC free article] [PubMed]
  • Borrow P, Lewicki H, Hahn BH, Shaw GM, Oldstone MB. Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J Virol. 1994 Sep;68(9):6103–6110. [PMC free article] [PubMed]
  • Pantaleo G, Demarest JF, Soudeyns H, Graziosi C, Denis F, Adelsberger JW, Borrow P, Saag MS, Shaw GM, Sekaly RP, et al. Major expansion of CD8+ T cells with a predominant V beta usage during the primary immune response to HIV. Nature. 1994 Aug 11;370(6489):463–467. [PubMed]
  • Moore JP, Cao Y, Ho DD, Koup RA. Development of the anti-gp120 antibody response during seroconversion to human immunodeficiency virus type 1. J Virol. 1994 Aug;68(8):5142–5155. [PMC free article] [PubMed]
  • Pantaleo G, Graziosi C, Demarest JF, Cohen OJ, Vaccarezza M, Gantt K, Muro-Cacho C, Fauci AS. Role of lymphoid organs in the pathogenesis of human immunodeficiency virus (HIV) infection. Immunol Rev. 1994 Aug;140:105–130. [PubMed]
  • Pantaleo G, Fauci AS. New concepts in the immunopathogenesis of HIV infection. Annu Rev Immunol. 1995;13:487–512. [PubMed]
  • Chen ZW, Kou ZC, Lekutis C, Shen L, Zhou D, Halloran M, Li J, Sodroski J, Lee-Parritz D, Letvin NL. T cell receptor V beta repertoire in an acute infection of rhesus monkeys with simian immunodeficiency viruses and a chimeric simian-human immunodeficiency virus. J Exp Med. 1995 Jul 1;182(1):21–31. [PMC free article] [PubMed]
  • Paul WE, Seder RA. Lymphocyte responses and cytokines. Cell. 1994 Jan 28;76(2):241–251. [PubMed]
  • Poli G, Fauci AS. The effect of cytokines and pharmacologic agents on chronic HIV infection. AIDS Res Hum Retroviruses. 1992 Feb;8(2):191–197. [PubMed]
  • Clerici M, Shearer GM. A TH1-->TH2 switch is a critical step in the etiology of HIV infection. Immunol Today. 1993 Mar;14(3):107–111. [PubMed]
  • Maggi E, Mazzetti M, Ravina A, Annunziato F, de Carli M, Piccinni MP, Manetti R, Carbonari M, Pesce AM, del Prete G, et al. Ability of HIV to promote a TH1 to TH0 shift and to replicate preferentially in TH2 and TH0 cells. Science. 1994 Jul 8;265(5169):244–248. [PubMed]
  • Graziosi C, Pantaleo G, Gantt KR, Fortin JP, Demarest JF, Cohen OJ, Sékaly RP, Fauci AS. Lack of evidence for the dichotomy of TH1 and TH2 predominance in HIV-infected individuals. Science. 1994 Jul 8;265(5169):248–252. [PubMed]
  • Meyaard L, Otto SA, Keet IP, van Lier RA, Miedema F. Changes in cytokine secretion patterns of CD4+ T-cell clones in human immunodeficiency virus infection. Blood. 1994 Dec 15;84(12):4262–4268. [PubMed]
  • Autran B, Legac E, Blanc C, Debré P. A Th0/Th2-like function of CD4+CD7- T helper cells from normal donors and HIV-infected patients. J Immunol. 1995 Feb 1;154(3):1408–1417. [PubMed]
  • Sinicco A, Biglino A, Sciandra M, Forno B, Pollono AM, Raiteri R, Gioannini P. Cytokine network and acute primary HIV-1 infection. AIDS. 1993 Sep;7(9):1167–1172. [PubMed]
  • Pantaleo G, Koenig S, Baseler M, Lane HC, Fauci AS. Defective clonogenic potential of CD8+ T lymphocytes in patients with AIDS. Expansion in vivo of a nonclonogenic CD3+CD8+DR+CD25- T cell population. J Immunol. 1990 Mar 1;144(5):1696–1704. [PubMed]
  • Pantaleo G, Graziosi C, Butini L, Pizzo PA, Schnittman SM, Kotler DP, Fauci AS. Lymphoid organs function as major reservoirs for human immunodeficiency virus. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9838–9842. [PMC free article] [PubMed]
  • Pantaleo G, Graziosi C, Demarest JF, Butini L, Montroni M, Fox CH, Orenstein JM, Kotler DP, Fauci AS. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature. 1993 Mar 25;362(6418):355–358. [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Ju ST, Panka DJ, Cui H, Ettinger R, el-Khatib M, Sherr DH, Stanger BZ, Marshak-Rothstein A. Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation. Nature. 1995 Feb 2;373(6513):444–448. [PubMed]
  • Delwart EL, Shpaer EG, Louwagie J, McCutchan FE, Grez M, Rübsamen-Waigmann H, Mullins JI. Genetic relationships determined by a DNA heteroduplex mobility assay: analysis of HIV-1 env genes. Science. 1993 Nov 19;262(5137):1257–1261. [PubMed]
  • Labrecque N, McGrath H, Subramanyam M, Huber BT, Sékaly RP. Human T cells respond to mouse mammary tumor virus-encoded superantigen: V beta restriction and conserved evolutionary features. J Exp Med. 1993 Jun 1;177(6):1735–1743. [PMC free article] [PubMed]
  • Rebai N, Pantaleo G, Demarest JF, Ciurli C, Soudeyns H, Adelsberger JW, Vaccarezza M, Walker RE, Sekaly RP, Fauci AS. Analysis of the T-cell receptor beta-chain variable-region (V beta) repertoire in monozygotic twins discordant for human immunodeficiency virus: evidence for perturbations of specific V beta segments in CD4+ T cells of the virus-positive twins. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1529–1533. [PMC free article] [PubMed]
  • Fan J, Bass HZ, Fahey JL. Elevated IFN-gamma and decreased IL-2 gene expression are associated with HIV infection. J Immunol. 1993 Nov 1;151(9):5031–5040. [PubMed]
  • Baier M, Werner A, Bannert N, Metzner K, Kurth R. HIV suppression by interleukin-16. Nature. 1995 Dec 7;378(6557):563–563. [PubMed]
  • Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995 Dec 15;270(5243):1811–1815. [PubMed]
  • Mackewicz CE, Yang LC, Lifson JD, Levy JA. Non-cytolytic CD8 T-cell anti-HIV responses in primary HIV-1 infection. Lancet. 1994 Dec 17;344(8938):1671–1673. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...