TY - JOUR
T1 - CD8 + T cells provide an immunologic signature of tuberculosis in young children
AU - Lancioni, Christina
AU - Nyendak, Melissa
AU - Kiguli, Sarah
AU - Zalwango, Sarah
AU - Mori, 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, La Shaunda
AU - Mudido-Musoke, Philipa
AU - Boom, W. Henry
AU - Lewinsohn, David M.
AU - Lewinsohn, Deborah A.
PY - 2012/1/15
Y1 - 2012/1/15
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 (<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.
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 (<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.
KW - CD8-positive T lymphocytes
KW - Child
KW - Enzyme-linked immunosorbent spot
KW - Infant
KW - Mycobacterium tuberculosis
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U2 - 10.1164/rccm.201107-1355OC
DO - 10.1164/rccm.201107-1355OC
M3 - Article
C2 - 22071329
AN - SCOPUS:84862908919
SN - 1073-449X
VL - 185
SP - 206
EP - 212
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 2
ER -