title: Characterization of CD4/CD8+ αβ and Vγ2Vδ2+ T cells in HIV-negative individuals with different Mycobacterium tuberculosis infection statuses.
abstract: BACKGROUND
  The immune responses of T cell subsets among patients with different Mycobacterium tuberculosis (M.tb) infection statuses [i.e., active tuberculosis (ATB), latent tuberculosis infection (LTBI) and non-infection (healthy control, HC)] have not been fully elucidated in HIV-negative individuals. Specifically, data are limiting in high tuberculosis epidemic regions in China. To investigate the distributions and functions of T cell subsets (i.e., CD3+, CD4+, CD8+ αβ and Vγ2Vδ2+ T cells) in HIV-negative subjects with different M.tb infection statuses, we conducted a case-control study that enrolled 125 participants, including ATB patients (n = 46), LTBI subjects (n = 34), and HC (n = 45).
  
  
  RESULTS
  An IFN-γ release assay (IGRA) was employed to screen LTBI subjects. Whole blood cell surface staining and flow cytometry were used to detect phenotypic distributions of T cells in the peripheral blood mononuclear cells (PBMCs) and tuberculous pleural fluid mononuclear cells (PFMCs). PPD and the phosphorylated antigen HMBPP were employed as stimulators for the detection of M.tb antigen-specific T cell functions via intracellular cytokine staining (ICS). The absolute numbers of T cell subsets, including CD3+ CD4+, CD3+ CD8+ αβ and Vγ2Vδ2+ T cells, were significantly reduced in active tuberculosis compared with latent tuberculosis or the healthy controls. Importantly, PPD-specific CD3+ CD4+ and CD3+ CD8+ αβ T cells and HMBPP-specific Vγ2Vδ2+ T cells in ATB patients were also significantly reduced compared to the LTBI/HC subjects (P<0.05). In contrast, the proportion of CD4+ T cells in PFMCs was higher compared to PBMCs, while CD8+ and Vγ2Vδ2+ T cells in PFMCs were lower compared to PBMCs (all P < 0.05). PPD-specific CD4+ T cells predominated among CD3+ T cells in PFMCs.
  
  
  CONCLUSIONS
  Cellular immune responses are impaired in ATB patients. Antigen-specific CD4+ T cell may migrate from the periphery to the lesion site, where they exert anti-tuberculosis functions.
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: 09111220004@fudan.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: vagus303@163.com.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pulmonary Diseases, Wuxi No. 5 People's Hospital, Wuxi 214005, China. Electronic address: oqinfang@163.com.
authors.forename: Qinfang
authors.initials: Q
authors.lastname: Ou
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: sh_leisen@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: 072105213@fudan.edu.cn.
authors.forename: Sen
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: jingee@fudan.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: w8061938@126.com.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Weng
authors.affiliation: Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois College of Medicine, 835 S. Wolcott Avenue, MC790 Chicago, IL 60612, United States. Electronic address: zchen@uic.edu.
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: zhangwenhong@fudan.edu.cn.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: lingyun26@fudan.edu.cn.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Shao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000276:immunology; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014376:Tuberculosis / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma
keywords: Active tuberculosis; Immune response; Interferon-gamma; Latent tuberculosis infection; T cell subsets