The potential impact of CD4+ T cell activation and enhanced Th1/Th2 cytokine ratio on HIV-1 secretion in the lungs of individuals with advanced AIDS and active pulmonary infection

Clin Immunol. 2011 May;139(2):142-54. doi: 10.1016/j.clim.2011.01.007. Epub 2011 Jan 27.

Abstract

Bronchoalveolar lavage fluid (BALF) provides a source of mucosal CD4(+) T cells. We investigated the physiological properties of T lymphocytes from BALF and blood and their role on the dynamic of HIV-1 replication among AIDS patients with active lung infections. Pulmonary CD4(+) T cells consist mainly of effector memory cells (CD45RO(+) and CCR7(-)) with increased expression of activation markers (HLA-DR(+) and CD69(+)) when compared to the blood counterpart. We observed a high frequency of BALF cells capable of secreting HIV-1-Ags suggesting that the local lung environment may support favorable conditions for CD4(+) T lymphocytes harboring HIV-1 DNA to initiate the viral cycle. Nevertheless, the high number of IFN-γ-producing cells and the predominance of Th1 immune response in the lung could limit the secretion of HIV-1 RNA. In conclusion, the capacity of activated CD4(+) T cells to produce HIV-1 is driven by both the level and quality of cellular activation in the lung.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / complications
  • Acquired Immunodeficiency Syndrome / immunology
  • Acquired Immunodeficiency Syndrome / virology*
  • Antigens, CD / metabolism
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Bronchoalveolar Lavage Fluid / virology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Cycloheximide / pharmacology
  • Cytokines / metabolism*
  • DNA, Viral / metabolism
  • HIV Antigens / metabolism
  • HIV-1 / isolation & purification
  • HIV-1 / physiology*
  • Humans
  • Immunophenotyping
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / virology
  • Lung / immunology
  • Lung / metabolism
  • Lung / virology*
  • Lymphocyte Activation / immunology*
  • RNA, Viral / metabolism
  • Receptors, CCR5
  • Receptors, CXCR4
  • Respiratory Tract Infections / etiology
  • Respiratory Tract Infections / immunology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocyte Subsets / virology
  • Viral Load / immunology
  • Viral Tropism / genetics
  • Virus Replication / drug effects
  • Virus Replication / immunology*

Substances

  • Antigens, CD
  • CXCR4 protein, human
  • Cytokines
  • DNA, Viral
  • HIV Antigens
  • RNA, Viral
  • Receptors, CCR5
  • Receptors, CXCR4
  • Interferon-gamma
  • Cycloheximide