title: Altered CD8(+) T cell frequency and function in tuberculous lymphadenitis.
abstract: CD8(+) T cells secreting Type1 and Type 17 cytokines and cytotoxic molecules play a major role in immunity and protection against pulmonary tuberculosis (PTB), although their role in tuberculous lymphadenitis (TBL) is not well known. To identify the distribution and function of CD8(+) T cells expressing Type1, Type 2 and Type 17 cytokines and cytotoxic molecules in TBL, we examined baseline and mycobacterial-antigen specific immune responses in the whole blood of individuals with PTB and compared them with TBL. TBL is characterized by elevated frequencies of baseline and mycobacterial-antigen stimulated CD8(+) T cells expressing Type 1 (IL-2 and TNFα) and Type 17 (IL-17A and IL-17F) cytokines in comparison to PTB individuals. In contrast, TBL individuals exhibited diminished frequency of CD8(+) T cells expressing perforin, granzyme B and CD107a. The blockade of IL-1R and IL-6R during antigenic stimulation resulted in significantly diminished frequencies of CD8(+) T cells expressing Type 1 and Type 17 cytokines in TBL. Therefore, our data suggest that TBL is characterized by an IL-1 and IL-6 dependent expansion of CD8(+) T cells expressing Type 1 and Type 17 cytokines as well as altered frequencies of cytotoxic molecules, reflecting an important association of these cells with the pathogenesis of TBL.
authors.affiliation: National Institutes of Health-International Center for Excellence in Research, Chennai, India; National Institute for Research in Tuberculosis, Chennai, India. Electronic address: pavankumarn@nirt.res.in.
authors.forename: Nathella Pavan
authors.initials: NP
authors.lastname: Kumar
authors.affiliation: Government Stanley Medical Hospital, Chennai, India.
authors.forename: Rathinam
authors.initials: R
authors.lastname: Sridhar
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Luke Elizabeth
authors.initials: LE
authors.lastname: Hanna
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Vaithilingam V
authors.initials: VV
authors.lastname: Banurekha
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Mohideen S
authors.initials: MS
authors.lastname: Jawahar
authors.affiliation: Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
authors.affiliation: National Institutes of Health-International Center for Excellence in Research, Chennai, India; Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D014388:Tuberculosis, Lymph Node / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000382:microbiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: CD8 T cells; Cytokines; Cytotoxic molecules; Lymphadenitis; Tuberculosis