T-cell activation is an immune correlate of risk in BCG vaccinated infants

被引：212

作者：

Fletcher, Helen A. ^{[1
,2
]}

Snowden, Margaret A. ^{[3
]}

Landry, Bernard ^{[3
]}

Rida, Wasima ^{[4
]}

Satti, Iman ^{[1
]}

Harris, Stephanie A. ^{[1
]}

Matsumiya, Magali ^{[1
]}

Tanner, Rachel ^{[1
]}

O'Shea, Matthew K. ^{[1
]}

Dheenadhayalan, Veerabadran ^{[3
]}

Bogardus, Leah ^{[3
]}

Stockdale, Lisa ^{[1
,2
]}

Marsay, Leanne ^{[5
]}

Chomka, Agnieszka ^{[6
]}

Harrington-Kandt, Rachel ^{[1
]}

Manjaly-Thomas, Zita-Rose ^{[1
]}

Naranbhai, Vivek ^{[7
]}

Stylianou, Elena ^{[1
]}

Darboe, Fatoumatta ^{[8
]}

Penn-Nicholson, Adam ^{[8
]}

Nemes, Elisa ^{[8
]}

Hatheril, Mark ^{[8
]}

Hussey, Gregory ^{[8
]}

Mahomed, Hassan ^{[8
]}

Tameris, Michele ^{[8
]}

McClain, J. Bruce ^{[3
]}

Evans, Thomas G. ^{[3
]}

Hanekom, Willem A. ^{[8
]}

Scriba, Thomas J. ^{[8
]}

McShane, Helen ^{[1
]}

机构：

[1] Univ Oxford, Jenner Inst, Nuffield Dept Med, Oxford OX3 7DQ, England

[2] London Sch Hyg & Trop Med, Dept Immunol & Infect, London W1CE7HT, England

[3] Aeras, Rockville, MD 20850 USA

[4] 1129 N Illinois St, Arlington, VA 22205 USA

[5] Univ Oxford, Dept Paediat, Oxford Vaccine Grp, Oxford OX3 7LE, England

[6] Univ Oxford, Kennedy Inst, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford OX3 7LF, England

[7] Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford OX37BN, England

[8] Univ Cape Town, Dept Paediat & Child Hlth, Inst Infect Dis & Mol Med, South African TB Vaccine Initiat, ZA-7935 Cape Town, South Africa

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

MYCOBACTERIUM-TUBERCULOSIS INFECTION; MULTICENTER AIDS COHORT; INTERFERON-GAMMA; DISEASE PROGRESSION; RECEPTOR DEFICIENCY; ANTIGEN-EXPRESSION; HIV-1; INFECTION; SOUTH-AFRICA; HLA-DR; MVA85A;

D O I：

10.1038/ncomms11290

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Vaccines to protect against tuberculosis (TB) are urgently needed. We performed a case-control analysis to identify immune correlates of TB disease risk in Bacille Calmette-Guerin (BCG) immunized infants from the MVA85A efficacy trial. Among 53 TB case infants and 205 matched controls, the frequency of activated HLA-DR+ CD4(+) T cells associates with increased TB disease risk (OR - 1.828, 95% CI - 1.25-2.68, P - 0.002, FDR = 0.04, conditional logistic regression). In an independent study of Mycobacterium tuberculosis-infected adolescents, activated HLA-DR+ CD4(+) T cells also associate with increased TB disease risk (OR = 1.387, 95% CI = 1.068-1.801, P = 0.014, conditional logistic regression). In infants, BCG-specific T cells secreting IFN-gamma associate with reduced risk of TB (OR = 0.502, 95% CI = 0.29-0.86, P = 0.013, FDR = 0.14). The causes and impact of T-cell activation on disease risk should be considered when designing and testing TB vaccine candidates for these populations.

引用

页数：10

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