Role of interleukin-10 in T helper cell dysfunction in asymptomatic individuals infected with the human immunodeficiency virus

Mario Clerici, Thomas A. Wynn, Jay A. Berzofsky, Stephen P. Blatt, Craig W. Hendrix, Alan Sher, Robert L. Coffman, Gene M. Shearer

Research output: Contribution to journalArticle

Abstract

The loss of T helper cell (TH) function in asymptomatic HIV type 1- infected individuals occurs before the decline in CD4+ T cells. At least part of the loss in TH function results from changes in immunoregulatory cytokine profiles. To investigate the role of IL-10 in such dysregulation, we tested whether: (a) expression of IL-10-specific mRNA would be upregulated in PBMC from asymptomatic, HIV-infected (HIV+) individuals; (b) PBMC from these same individuals would produce increased levels of IL-10 when stimulated in vitro with phytohemagglutinin; and (c) defective antigen-specific TH function could be restored by anti-IL-10 antibody. We observed that IL-10-specific mRNA was marginally upregulated, and increased levels of IL-10 were produced by PBMC from HIV+ individuals compared with PBMC from uninfected individuals. Those individuals whose TH function was more severely compromised produced higher levels of IL-10. Additionally, defective antigen- specific TH function in vitro could be reversed by anti-IL-10 antibody, including the response to HIV envelope synthetic peptides. Furthermore, the antigen-specific TH responses of HIV-uninfected PBMC could be reduced with IL-10, a process reversed by anti-IL-10. These results confirm that the early loss of TH function in HIV+ individuals is due at least in part to cytokine- induced immune dysregulation, and support the hypothesis of a switch from a predominant type I state to a predominant type 2 condition in HIV infection.

Original languageEnglish
Pages (from-to)768-775
Number of pages8
JournalJournal of Clinical Investigation
Volume93
Issue number2
Publication statusPublished - Feb 1994

Keywords

  • cytokines
  • human immunodeficiency virus infection
  • interleukin-10
  • interleukin-2
  • T lymphocytes

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Role of interleukin-10 in T helper cell dysfunction in asymptomatic individuals infected with the human immunodeficiency virus'. Together they form a unique fingerprint.

  • Cite this

    Clerici, M., Wynn, T. A., Berzofsky, J. A., Blatt, S. P., Hendrix, C. W., Sher, A., Coffman, R. L., & Shearer, G. M. (1994). Role of interleukin-10 in T helper cell dysfunction in asymptomatic individuals infected with the human immunodeficiency virus. Journal of Clinical Investigation, 93(2), 768-775.