RT Journal Article
T1 Tuberculosis Therapy Modifies the Cytokine Profile, Maturation State, and Expression of Inhibitory Molecules on Mycobacterium tuberculosis-Specific CD4+ T-Cells.
A1 Saharia, Kapil K
A1 Petrovas, Constantinos
A1 Ferrando-Martinez, Sara
A1 Leal, Manuel
A1 Luque, Rafael
A1 Ive, Prudence
A1 Luetkemeyer, Anne
A1 Havlir, Diane
A1 Koup, Richard A
K1 Tuberculosis
K1 HIV Coinfection
K1 CD4 T-Cells
K1 Cytokine Profile
K1 Inhibitory Molecules
K1 CTLA-4 Expression
K1 PD-1 Expression
K1 TB Treatment
K1 Effector Memory T-Cells
AB Little is known about the expression of inhibitory molecules cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed-death-1 (PD-1) on Mycobacterium tuberculosis (Mtb)-specific CD4 T-cells and how their expression is impacted by TB treatment. Cryopreserved PBMCs from HIV-TB co-infected and TB mono-infected patients with untreated and treated tuberculosis (TB) disease were stimulated for six hours with PPD and stained. Using polychromatic flow cytometry, we characterized the differentiation state, cytokine profile, and inhibitory molecule expression on PPD-specific CD4 T-cells. In our HIV-TB co-infected cohort, TB treatment increased the proportion of PPD-specific CD4 T-cells co-producing IFN-γ+IL-2+TNF-α+ and IFN-γ+IL-2+ (p = 0.0004 and p = 0.0002, respectively) while decreasing the proportion of PPD-specific CD4 T-cells co-producing IFN-γ+MIP1-β+TNF-α+ and IFN-γ+MIP1-β+. The proportion of PPD-specific CD4 T-cells expressing an effector memory phenotype decreased (63.6% vs 51.6%, p = 0.0015) while the proportion expressing a central memory phenotype increased (7.8% vs. 21.7%, p = 0.001) following TB treatment. TB treatment reduced the proportion of PPD-specific CD4 T-cells expressing CTLA-4 (72.4% vs. 44.3%, p = 0.0005) and PD-1 (34.5% vs. 29.2%, p = 0.03). Similar trends were noted in our TB mono-infected cohort. TB treatment alters the functional profile of Mtb-specific CD4 T-cells reflecting shifts towards a less differentiated maturational profile and decreases PD-1 and CTLA-4 expression. These could serve as markers of reduced mycobacterial burden. Further study is warranted.
PB Public Library of Science
YR 2016
FD 2016-07-01
LK http://hdl.handle.net/10668/10229
UL http://hdl.handle.net/10668/10229
LA en
NO Saharia KK, Petrovas C, Ferrando-Martinez S, Leal M, Luque R, Ive P, et al.  Tuberculosis Therapy Modifies the Cytokine Profile, Maturation State, and Expression of Inhibitory Molecules on Mycobacterium tuberculosis-Specific CD4+ T-Cells. PLoS One. 2016 Jul 1;11(7):e0158262.
DS RISalud
RD Aug 4, 2025