title: CD4+ T cell polyfunctional profile in HIV-TB coinfection are similar between individuals with latent and active TB infection.
abstract: CD4+ T cell counts of HIV-infected individuals with pulmonary TB (PTB) are higher than with other opportunistic infections suggesting that progression to PTB is not merely due to T cell depletion but also dysfunction. There are limited data examining T cell functional signatures in human HIV-TB co-infection particularly in PTB which accounts for about 80% of active TB disease overall. We examined a cohort of HIV-infected anti-retroviral naïve individuals in Kampala, Uganda, a TB endemic area using multiparametric flow cytometry analysis to determine IFN-γ, IL-2, IL-17, and TNF-α production in CD4+ memory T cell subsets. The cytokine frequency and polyfunctionality profile of Mycobacterium tuberculosis (MTB)-specific CD4+ T cells in HIV-infected persons with latent TB infection (LTBI) or PTB is comparable. This similarity suggests that LTBI may represent a smoldering state of persistent MTB replication rather than dormant infection. This may be a contributory mechanism to the significantly increased risk of progression to PTB in this population.
authors.affiliation: Division of Infectious Diseases and HIV Medicine, University Hospitals of Cleveland and Case Western Reserve University School of Medicine, 10900 Euclid Ave, BRB 1022, Cleveland, OH, 44106-4984, USA; Geriatric Research Center Clinical Center (GRECC), Louis Stokes Cleveland VA, Cleveland, OH, 44106, USA. Electronic address: David.Canaday@case.edu.
authors.forename: David H
authors.initials: DH
authors.lastname: Canaday
authors.affiliation: Division of Infectious Diseases and HIV Medicine, University Hospitals of Cleveland and Case Western Reserve University School of Medicine, 10900 Euclid Ave, BRB 1022, Cleveland, OH, 44106-4984, USA. Electronic address: sxs973@case.edu.
authors.forename: Sankar
authors.initials: S
authors.lastname: Sridaran
authors.affiliation: Division of Infectious Diseases and HIV Medicine, University Hospitals of Cleveland and Case Western Reserve University School of Medicine, 10900 Euclid Ave, BRB 1022, Cleveland, OH, 44106-4984, USA; Geriatric Research Center Clinical Center (GRECC), Louis Stokes Cleveland VA, Cleveland, OH, 44106, USA. Electronic address: pujavanepps1@gmail.com.
authors.forename: Puja
authors.initials: P
authors.lastname: Van Epps
authors.affiliation: Division of Infectious Diseases and HIV Medicine, University Hospitals of Cleveland and Case Western Reserve University School of Medicine, 10900 Euclid Ave, BRB 1022, Cleveland, OH, 44106-4984, USA. Electronic address: hxa11@case.edu.
authors.forename: Htin
authors.initials: H
authors.lastname: Aung
authors.affiliation: Geriatric Research Center Clinical Center (GRECC), Louis Stokes Cleveland VA, Cleveland, OH, 44106, USA; Case Western Reserve University Frances Payne Bolton School of Nursing, Cleveland, OH, 44106, USA. Electronic address: christopher.burant@va.gov.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Burant
authors.affiliation: Department of Medicine, Makerere University, PO Box 7072, Kampala, Uganda. Electronic address: mnsereko@mucwru.or.ug.
authors.forename: Mary
authors.initials: M
authors.lastname: Nsereko
authors.affiliation: Department of Medicine, Makerere University, PO Box 7072, Kampala, Uganda. Electronic address: hmk@chs.mak.ac.ug.
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, 3610 Hamilton Walk, Philadelphia, PA, 19104, USA. Electronic address: betts@mail.med.upenn.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Betts
authors.affiliation: Division of Infectious Diseases and HIV Medicine, University Hospitals of Cleveland and Case Western Reserve University School of Medicine, 10900 Euclid Ave, BRB 1022, Cleveland, OH, 44106-4984, USA. Electronic address: zxt2@case.edu.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Toossi
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000821:virology; D060085:Coinfection; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007156:Immunologic Memory; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000382:microbiology; D014454:Uganda
chemical_list: D016207:Cytokines
keywords: CD4+ T cell; HIV-1; Polyfunctionality; Tuberculosis