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

Publication ,  Journal Article
Seshadri, C; Lin, L; Scriba, TJ; Peterson, G; Freidrich, D; Frahm, N; DeRosa, SC; Moody, DB; Prandi, J; Gilleron, M; Mahomed, H; Jiang, W ...
Published in: J Immunol
November 15, 2015

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.

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

November 15, 2015

Volume

195

Issue

10

Start / End Page

4595 / 4603

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Tuberculosis, Pulmonary
  • South Africa
  • Mycobacterium tuberculosis
  • Membrane Lipids
  • Male
  • Lymphocyte Activation
  • K562 Cells
  • Interleukin-2
  • Interferon-gamma
 

Citation

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Seshadri, C., Lin, L., Scriba, T. J., Peterson, G., Freidrich, D., Frahm, N., … Hawn, T. R. (2015). T Cell Responses against Mycobacterial Lipids and Proteins Are Poorly Correlated in South African Adolescents. J Immunol, 195(10), 4595–4603. https://doi.org/10.4049/jimmunol.1501285
Seshadri, Chetan, Lin Lin, Thomas J. Scriba, Glenna Peterson, David Freidrich, Nicole Frahm, Stephen C. DeRosa, et al. “T Cell Responses against Mycobacterial Lipids and Proteins Are Poorly Correlated in South African Adolescents.J Immunol 195, no. 10 (November 15, 2015): 4595–4603. https://doi.org/10.4049/jimmunol.1501285.
Seshadri C, Lin L, Scriba TJ, Peterson G, Freidrich D, Frahm N, et al. T Cell Responses against Mycobacterial Lipids and Proteins Are Poorly Correlated in South African Adolescents. J Immunol. 2015 Nov 15;195(10):4595–603.
Seshadri, Chetan, et al. “T Cell Responses against Mycobacterial Lipids and Proteins Are Poorly Correlated in South African Adolescents.J Immunol, vol. 195, no. 10, Nov. 2015, pp. 4595–603. Pubmed, doi:10.4049/jimmunol.1501285.
Seshadri C, Lin L, Scriba TJ, Peterson G, Freidrich D, Frahm N, DeRosa SC, Moody DB, Prandi J, Gilleron M, Mahomed H, Jiang W, Finak G, Hanekom WA, Gottardo R, McElrath MJ, Hawn TR. T Cell Responses against Mycobacterial Lipids and Proteins Are Poorly Correlated in South African Adolescents. J Immunol. 2015 Nov 15;195(10):4595–4603.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

November 15, 2015

Volume

195

Issue

10

Start / End Page

4595 / 4603

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Tuberculosis, Pulmonary
  • South Africa
  • Mycobacterium tuberculosis
  • Membrane Lipids
  • Male
  • Lymphocyte Activation
  • K562 Cells
  • Interleukin-2
  • Interferon-gamma