CD8 + T cells provide an immunologic signature of tuberculosis in young children

Christina Lancioni, Melissa Nyendak, Sarah Kiguli, Sarah Zalwango, Tomi Mori, Harriet Mayanja-Kizza, Stephen Balyejusa, Megan Null, Joy Baseke, Deo Mulindwa, Laura Byrd, Gwendolyn Swarbrick, Christine Scott, Denise F. Johnson, La Shaunda Malone, Philipa Mudido-Musoke, W. Henry Boom, David M. Lewinsohn, Deborah A. Lewinsohn

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

The immunologic events surrounding primary Mycobacterium tuberculosis infection and development of tuberculosis remain controversial. Young children who develop tuberculosis do so quickly after first exposure, thus permitting study of immune response to primary infection and disease. We hypothesized that M. tuberculosis-specific CD81 T cells are generated in response to high bacillary loads occurring during tuberculosis. Objectives: To determine if M. tuberculosis-specific T cells are generated among healthy children exposed to M. tuberculosis and children with tuberculosis. Methods: Enzyme-linked immunosorbent spot assays were used to measure IFN-γ production in response to M.tuberculosis-specific proteins ESAT-6/CFP-10 by peripheral blood mononuclear cells and CD8 + T cells isolated from Ugandan children hospitalized with tuberculosis (n = 96) or healthy tuberculosis contacts (n = 62). Measurements and Main Results: The proportion of positive CD8 +T-cell assays and magnitude of CD8 + T-cell responses were significantly greater among young (<5 yr) tuberculosis cases compared with young contacts (P = 0.02, Fisher exact test, P = 0.01, Wilcoxon rank-sum, respectively). M. tuberculosis-specific T-cell responses measured in peripheral blood mononuclear cells were equivalent between groups. Conclusions: Among young children, M. tuberculosis-specific CD8 +T cells develop in response to high bacillary loads, as occurs during tuberculosis, andareunlikely to be found after M. tuberculosis exposure. T-cell responses measured in peripheral blood mononuclear cells are generated after M. tuberculosis exposure alone, and thus cannot distinguish exposure from disease. In young children, IFN-γ-producing M. tuberculosis-specific CD8 + T cells provide an immunologic signature of primary M. tuberculosis infection resulting in disease.

Original languageEnglish (US)
Pages (from-to)206-212
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume185
Issue number2
DOIs
StatePublished - Jan 15 2012

Keywords

  • CD8-positive T lymphocytes
  • Child
  • Enzyme-linked immunosorbent spot
  • Infant
  • Mycobacterium tuberculosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Lancioni, C., Nyendak, M., Kiguli, S., Zalwango, S., Mori, T., Mayanja-Kizza, H., Balyejusa, S., Null, M., Baseke, J., Mulindwa, D., Byrd, L., Swarbrick, G., Scott, C., Johnson, D. F., Malone, L. S., Mudido-Musoke, P., Boom, W. H., Lewinsohn, D. M., & Lewinsohn, D. A. (2012). CD8 + T cells provide an immunologic signature of tuberculosis in young children. American journal of respiratory and critical care medicine, 185(2), 206-212. https://doi.org/10.1164/rccm.201107-1355OC