Lymphocyte-dependent inhibition of growth of virulent Mycobacterium tuberculosis H37Rv within human monocytes: Requirement for CD4+ T cells in purified protein derivative-positive, but not in purified protein derivative- negative subjects

Richard F. Silver, Qing Li, W. Henry Boom, Jerrold J. Ellner

Research output: Contribution to journalArticle

Abstract

Protective human immunity to Mycobacterium tuberculosis (M. tb) has proven difficult to characterize, in part because of technical obstacles to in vitro infection of human cells with virulent M. tb. We established a reproducible method of infecting human monocytes (MN) with the virulent M. tb strain H37Rv that did not reduce MN viability. TNF-α had no effect on replication of H37Rv within MN, and IFN-γ mediated only a 1.9-fold reduction in bacterial growth. In contrast, nonadherent cells (NAC) from purified protein derivative (PPD)-positive and PPD-negative subjects reduced intracellular growth of H37Rv by 6- and 10.6-fold, respectively (p = 0.007 and p = 0.005). CD4+ T cells were essential to growth inhibition mediated by NAC of PPD-positive subjects, whereas containment of M. tb by NAC of PPD- negative subjects did not require CD4+ cells. CD8+ T cells did not contribute to protection mediated by NAC of either group. Supernatants of cocultured H37Rv-infected MN and NAC only partially reduced intracellular growth of M. tb despite containing nanogram concentrations of TNF-α and IFN- γ. Neutralizing antibodies to TNF-α, IFN-γ, and IL-12 failed to affect the NAC-mediated growth limitation. NAC treated with emetine retained approximately 40% of their capacity to contain intracellular H37Rv, however. These studies indicate that protective human recall responses to M. tb are mediated primarily by CD4+ T cells, whereas CD4-CD8- lymphocytes may contribute to innate immunity to M. tb. The ability of NAC to activate M. tb- infected MN is only partly attributable to soluble mediators and may also involve contact-mediated mechanisms.

Original languageEnglish (US)
Pages (from-to)2408-2417
Number of pages10
JournalJournal of Immunology
Volume160
Issue number5
StatePublished - Mar 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Lymphocyte-dependent inhibition of growth of virulent Mycobacterium tuberculosis H37Rv within human monocytes: Requirement for CD4+ T cells in purified protein derivative-positive, but not in purified protein derivative- negative subjects'. Together they form a unique fingerprint.

  • Cite this