title: Treatment of latent tuberculosis infection induces changes in multifunctional Mycobacterium tuberculosis-specific CD4+ T cells.
abstract: To ascertain whether multiparametric flow cytometry assessment of multifunctional Mycobacterium tuberculosis (Mtb)-specific CD4(+) and CD8(+) T cells can distinguish between untreated and treated patients with latent tuberculosis infection (LTBI), we enrolled 14 LTBI subjects treated with isoniazid (INH) therapy, 16 untreated LTBI patients, and 25 healthy controls. The analysis of mono-functional CD4(+) and CD8(+) T cells producing single cytokines showed significant differences only between uninfected and infected LTBI subjects (both treated and untreated). Conversely, the analysis of multifunctional CD4(+) T cells revealed a significant reduction in the frequency of two CD4(+) T cells subsets, those producing IFN-γ, IL-2, and TNF-α simultaneously (triple positive; p = 0.005) and those producing IL-2 alone (p = 0.0359), as well as a shift towards T cells producing only one cytokine in treated as compared to untreated LTBI subjects. Assigning a triple-positive CD4(+) T cells a cut-off >0.082 %, 94 % of untreated LTBI patients were scored as positive, as compared to only 28 % of treated LTBI patients and none of the healthy controls. No significant differences between untreated and treated LTBI subjects in terms of Mtb-specific CD8(+) T cell cytokine profiles (p > 0.05) were identified. The significant changes in the cytokine profiles of Mtb-specific T cells after INH therapy suggest that analysis of multifunctional T cells may be a promising means for the monitoring of LTBI treatment success.
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 1, 00185, Rome, Italy. ilariasauzullo@libero.it.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Sauzullo
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 1, 00185, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Mengoni
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 1, 00185, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mascia
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 1, 00185, Rome, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Rossi
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 1, 00185, Rome, Italy.|Infectious Diseases Unit, Fondazione Eleonora Lorillard Spencer Cenci, Sapienza University, Latina, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Lichtner
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 1, 00185, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vullo
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 1, 00185, Rome, Italy.|Infectious Diseases Unit, Fondazione Eleonora Lorillard Spencer Cenci, Sapienza University, Latina, Italy.
authors.forename: Claudio M
authors.initials: CM
authors.lastname: Mastroianni
mesh_terms: D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage; D055985:Latent Tuberculosis / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012189:Retrospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D000995:Antitubercular Agents; D016207:Cytokines; D007538:Isoniazid
keywords: Cytokines; Intracellular cytokine flow cytometry; Latent tuberculosis infection; M. tuberculosis; Multifunctional T cells; TB treatment