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Thymic microenvironment induces HIV expression. Physiologic secretion of IL-6 by thymic epithelial cells up-regulates virus expression in chronically infected cells.

Publication ,  Journal Article
Schnittman, SM; Singer, KH; Greenhouse, JJ; Stanley, SK; Whichard, LP; Le, PT; Haynes, BF; Fauci, AS
Published in: J Immunol
October 15, 1991

The hallmark of infection with HIV-1 is progressive depletion and qualitative dysfunction of the CD4+ Th cell population in infected individuals. Clinical trials of antiretroviral agents have shown that, despite suppression of virus replication, regeneration of the T cell pool does not occur. One proposed explanation for the defective regenerative capacity of the CD4+ T cell pool is infection of early T lymphocyte progenitors or stem cells. An additional explanation could be failure of cells of the intrathymic microenvironment (thymic epithelial (TE) cells) to carry out critical nurturing functions for developing thymocytes, i.e., secretion of thymocyte-trophic cytokines and expression of adhesion molecules. This study examines the effect of HIV on cultured TE cells and determines the role of TE cells in the regulation of viral expression in chronically HIV-infected cells. We found no evidence of infection of TE cells after exposure to HIV-1. However, normal human serum induced secretion of IL-6 by TE cells; induction of TE IL-6 was partially blocked by anti-IFN-gamma antibodies. Moreover, supernatants from TE cells maintained in normal human serum up-regulated HIV replication in chronically HIV-1-infected cells. Because intrathymic T cell precursors can be infected with HIV and T cell precursors come into close contact with TE cells in the thymus, IL-6 secreted by TE cells during normal intrathymic development may induce HIV expression in infected thymocytes in vivo and promote the intrathymic spread of HIV.

Duke Scholars

Published In

J Immunol

ISSN

0022-1767

Publication Date

October 15, 1991

Volume

147

Issue

8

Start / End Page

2553 / 2558

Location

United States

Related Subject Headings

  • Virus Replication
  • Up-Regulation
  • Thymus Gland
  • Interleukin-6
  • Interferon-gamma
  • Immunology
  • Humans
  • HIV
  • Epithelium
  • Child
 

Citation

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Schnittman, S. M., Singer, K. H., Greenhouse, J. J., Stanley, S. K., Whichard, L. P., Le, P. T., … Fauci, A. S. (1991). Thymic microenvironment induces HIV expression. Physiologic secretion of IL-6 by thymic epithelial cells up-regulates virus expression in chronically infected cells. J Immunol, 147(8), 2553–2558.
Schnittman, S. M., K. H. Singer, J. J. Greenhouse, S. K. Stanley, L. P. Whichard, P. T. Le, B. F. Haynes, and A. S. Fauci. “Thymic microenvironment induces HIV expression. Physiologic secretion of IL-6 by thymic epithelial cells up-regulates virus expression in chronically infected cells.J Immunol 147, no. 8 (October 15, 1991): 2553–58.
Schnittman SM, Singer KH, Greenhouse JJ, Stanley SK, Whichard LP, Le PT, et al. Thymic microenvironment induces HIV expression. Physiologic secretion of IL-6 by thymic epithelial cells up-regulates virus expression in chronically infected cells. J Immunol. 1991 Oct 15;147(8):2553–8.
Schnittman SM, Singer KH, Greenhouse JJ, Stanley SK, Whichard LP, Le PT, Haynes BF, Fauci AS. Thymic microenvironment induces HIV expression. Physiologic secretion of IL-6 by thymic epithelial cells up-regulates virus expression in chronically infected cells. J Immunol. 1991 Oct 15;147(8):2553–2558.

Published In

J Immunol

ISSN

0022-1767

Publication Date

October 15, 1991

Volume

147

Issue

8

Start / End Page

2553 / 2558

Location

United States

Related Subject Headings

  • Virus Replication
  • Up-Regulation
  • Thymus Gland
  • Interleukin-6
  • Interferon-gamma
  • Immunology
  • Humans
  • HIV
  • Epithelium
  • Child