Depletion of CD4+ T cells causes reactivation of murine persistent tuberculosis despite continued expression of interferon γ and nitric oxide synthase 2

Charles A. Scanga, V. P. Mohan, Keming Yu, Heather Joseph, Kathryn E. Tanaka, John Chan, JoAnne L. Flynn

Research output: Contribution to journalArticle

251 Citations (Scopus)

Abstract

Tuberculosis is a major cause of death in much of the world. Current estimates are that one-third of the world's population is infected with Mycobacterium tuberculosis. Most infected persons control the infection but in many cases may not eliminate the organism. Reactivation of this clinically latent infection is responsible for a large proportion of active tuberculosis cases. A major risk factor for reactivation of latent tuberculosis is HIV infection, suggesting a role for the CD4+ T cell subset in maintaining the latent persistent infection. In this study, we tested the requirement for CD4+ T cells in preventing reactivation in a routine model of latent tuberculosis. Antibody-mediated depletion of CD4+ T cells resulted in rapid reactivation of a persistent infection, with dramatically increased bacterial numbers in the organs, increased pathology in the lungs, and decreased survival. Although CD4+ T cells are believed to be a major source of interferon (IFN)-γ, expression of the gene for IFN-γ in the lungs of CD4+ T cell-depleted mice was similar to that in control mice. In addition, inducible nitric oxide synthase production and activity was unimpaired after CD4+ T cell depletion, indicating that macrophage activation was present even during CD4+ T cell deficiency. These data indicate that CD4+ T cells are necessary to prevent reactivation but may have roles in addition to IFN-γ production and macrophage activation in controlling a persistent tuberculous infection.

Original languageEnglish (US)
Pages (from-to)347-358
Number of pages12
JournalJournal of Experimental Medicine
Volume192
Issue number3
DOIs
StatePublished - Aug 7 2000

Fingerprint

Nitric Oxide Synthase
Interferons
Tuberculosis
T-Lymphocytes
Latent Tuberculosis
Macrophage Activation
Infection
Lung
T-Lymphocyte Subsets
Nitric Oxide Synthase Type II
Infection Control
Mycobacterium tuberculosis
HIV Infections
Cause of Death
Pathology
Gene Expression
Survival
Antibodies
Population

Keywords

  • Bacterial infection
  • Lung
  • Macrophage
  • Mycobacterium tuberculosis
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Immunology

Cite this

Depletion of CD4+ T cells causes reactivation of murine persistent tuberculosis despite continued expression of interferon γ and nitric oxide synthase 2. / Scanga, Charles A.; Mohan, V. P.; Yu, Keming; Joseph, Heather; Tanaka, Kathryn E.; Chan, John; Flynn, JoAnne L.

In: Journal of Experimental Medicine, Vol. 192, No. 3, 07.08.2000, p. 347-358.

Research output: Contribution to journalArticle

Scanga, Charles A. ; Mohan, V. P. ; Yu, Keming ; Joseph, Heather ; Tanaka, Kathryn E. ; Chan, John ; Flynn, JoAnne L. / Depletion of CD4+ T cells causes reactivation of murine persistent tuberculosis despite continued expression of interferon γ and nitric oxide synthase 2. In: Journal of Experimental Medicine. 2000 ; Vol. 192, No. 3. pp. 347-358.
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