T Cell Responses against Mycobacterial Lipids and Proteins Are Poorly Correlated in South African Adolescents.

Journal of immunology (Baltimore, Md. : 1950) 2015 Nov 15

filter terms:

Human T cells are activated by both peptide and nonpeptide Ags produced by Mycobacterium tuberculosis. T cells recognize cell wall lipids bound to CD1 molecules, but effector functions of CD1-reactive T cells have not been systematically assessed in M. tuberculosis-infected humans. It is also not known how these features correlate with T cell responses to secreted protein Ags. We developed a flow cytometric assay to profile CD1-restricted T cells ex vivo and assessed T cell responses to five cell wall lipid Ags in a cross-sectional study of 19 M. tuberculosis-infected and 22 M. tuberculosis-uninfected South African adolescents. We analyzed six T cell functions using a recently developed computational approach for flow cytometry data in high dimensions. We compared these data with T cell responses to five protein Ags in the same cohort. We show that CD1b-restricted T cells producing antimycobacterial cytokines IFN-γ and TNF-α are detectable ex vivo in CD4(+), CD8(+), and CD4(-)CD8(-) T cell subsets. Glucose monomycolate was immunodominant among lipid Ags tested, and polyfunctional CD4 T cells specific for this lipid simultaneously expressed CD40L, IFN-γ, IL-2, and TNF-α. Lipid-reactive CD4(+) T cells were detectable at frequencies of 0.001-0.01%, and this did not differ by M. tuberculosis infection status. Finally, CD4 T cell responses to lipids were poorly correlated with CD4 T cell responses to proteins (Spearman rank correlation -0.01; p = 0.95). These results highlight the functional diversity of CD1-restricted T cells circulating in peripheral blood as well as the complementary nature of T cell responses to mycobacterial lipids and proteins. Our approach enables further population-based studies of lipid-specific T cell responses during natural infection and vaccination. Copyright © 2015 by The American Association of Immunologists, Inc.

Citation

Chetan Seshadri, Lin Lin, Thomas J Scriba, Glenna Peterson, David Freidrich, Nicole Frahm, Stephen C DeRosa, D Branch Moody, Jacques Prandi, Martine Gilleron, Hassan Mahomed, Wenxin Jiang, Greg Finak, Willem A Hanekom, Raphael Gottardo, M Juliana McElrath, Thomas R Hawn. T Cell Responses against Mycobacterial Lipids and Proteins Are Poorly Correlated in South African Adolescents. Journal of immunology (Baltimore, Md. : 1950). 2015 Nov 15;195(10):4595-603