Tim-3-Expressing CD4+ and CD8+ T Cells in Human Tuberculosis (TB) Exhibit Polarized Effector Memory Phenotypes and Stronger Anti-TB Effector Functions

• DOI: 10.1371/journal.ppat.1002984
• Publication Date: 2012-11-08T17:20:15Z
• Authors: Yueqin Qiu; Jianbo Chen; Hongying Liao; Yan Zhang; Hua Wang; Shaoyuan Li; Yanfen Luo; Danyun Fang; Guobao Li; Boping Zhou; Ling Shen; Crystal Y. Chen; Dan Huang; Jiye Cai; Kaiyuan Cao; Lifang Jiang; Gucheng Zeng; Zheng W. Chen
• Keywords: Male; QH301-705.5; Tumor Necrosis Factor-alpha; Membrane Proteins; RC581-607; CD8-Positive T-Lymphocytes; Th1 Cells; Lymphocyte Activation; 3. Good health; Interferon-gamma; 03 medical and health sciences; 0302 clinical medicine; Gene Expression Regulation; Humans; Tuberculosis; Female; Immunologic diseases. Allergy; Biology (General); Hepatitis A Virus Cellular Receptor 2; Immunologic Memory; Research Article; Signal Transduction

T-cell immune responses modulated by immunoglobulin and mucin domain-containing molecule 3 (Tim-3) during Mycobacterium tuberculosis (Mtb) infection in humans remain poorly understood. Here, we found that active TB patients exhibited increases numbers of Tim-3-expressing CD4+ CD8+ T cells, which preferentially displayed polarized effector memory phenotypes. Consistent with phenotypes, Tim-3+CD4+ Tim-3+CD8+ subsets showed greater functions for producing Th1/Th22 cytokines CTL molecules than Tim-3− counterparts, cells more apparently limited intracellular Mtb replication macrophages. The increased consisted cellular activation signaling as expressed much higher levels phosphorylated p38, stat3, stat5, Erk1/2 Tim-3- controls. Mechanistic experiments siRNA silencing Tim-3 or soluble treatment interfering membrane Tim-3-ligand interaction reduced de novo production IFN-γ TNF-α cells. Furthermore, stimulation pathways antibody cross-linking augmented function suggesting helped to drive stronger patients. This study therefore uncovered a previously unknown mechanism regulated Tim-3, findings may have implications potential intervention TB.