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

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

Research output: Contribution to journalArticle

36 Citations (Scopus)

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 (+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

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Mycobacterium tuberculosis
Tuberculosis
T-Lymphocytes
Mycobacterium Infections
Blood Cells
Hospitalized Child
Enzyme-Linked Immunosorbent Assay
Infection
Proteins

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

Cite this

CD8 + T cells provide an immunologic signature of tuberculosis in young children. / Lancioni, Christina; Nyendak, Melissa; Kiguli, Sarah; Zalwango, Sarah; Mori, Motomi (Tomi); Mayanja-Kizza, Harriet; Balyejusa, Stephen; Null, Megan; Baseke, Joy; Mulindwa, Deo; Byrd, Laura; Swarbrick, Gwendolyn; Scott, Christine; Johnson, Denise F.; Malone, LaShaunda; Mudido-Musoke, Philipa; Boom, W. Henry; Lewinsohn, David; Lewinsohn, Deborah.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 185, No. 2, 15.01.2012, p. 206-212.

Research output: Contribution to journalArticle

Lancioni, C, Nyendak, M, Kiguli, S, Zalwango, S, Mori, MT, Mayanja-Kizza, H, Balyejusa, S, Null, M, Baseke, J, Mulindwa, D, Byrd, L, Swarbrick, G, Scott, C, Johnson, DF, Malone, L, Mudido-Musoke, P, Boom, WH, Lewinsohn, D & Lewinsohn, D 2012, 'CD8 + T cells provide an immunologic signature of tuberculosis in young children', American Journal of Respiratory and Critical Care Medicine, vol. 185, no. 2, pp. 206-212. https://doi.org/10.1164/rccm.201107-1355OC
Lancioni, Christina ; Nyendak, Melissa ; Kiguli, Sarah ; Zalwango, Sarah ; Mori, Motomi (Tomi) ; Mayanja-Kizza, Harriet ; Balyejusa, Stephen ; Null, Megan ; Baseke, Joy ; Mulindwa, Deo ; Byrd, Laura ; Swarbrick, Gwendolyn ; Scott, Christine ; Johnson, Denise F. ; Malone, LaShaunda ; Mudido-Musoke, Philipa ; Boom, W. Henry ; Lewinsohn, David ; Lewinsohn, Deborah. / CD8 + T cells provide an immunologic signature of tuberculosis in young children. In: American Journal of Respiratory and Critical Care Medicine. 2012 ; Vol. 185, No. 2. pp. 206-212.
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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 (+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.",
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AU - Nyendak, Melissa

AU - Kiguli, Sarah

AU - Zalwango, Sarah

AU - Mori, Motomi (Tomi)

AU - Mayanja-Kizza, Harriet

AU - Balyejusa, Stephen

AU - Null, Megan

AU - Baseke, Joy

AU - Mulindwa, Deo

AU - Byrd, Laura

AU - Swarbrick, Gwendolyn

AU - Scott, Christine

AU - Johnson, Denise F.

AU - Malone, LaShaunda

AU - Mudido-Musoke, Philipa

AU - Boom, W. Henry

AU - Lewinsohn, David

AU - Lewinsohn, Deborah

PY - 2012/1/15

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N2 - 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 (+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.

AB - 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 (+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.

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