title: Dynamic relationship between IFN-gamma and IL-2 profile of Mycobacterium tuberculosis-specific T cells and antigen load.
abstract: Distinct IFN-gamma and IL-2 profiles of Ag-specific CD4(+) T cells have recently been associated with different clinical disease states and Ag loads in viral infections. We assessed the kinetics and functional profile of Mycobacterium tuberculosis Ag-specific T cells secreting IFN-gamma and IL-2 in 23 patients with untreated active tuberculosis when bacterial and Ag loads are high and after curative treatment, when Ag load is reduced. The frequencies of M. tuberculosis Ag-specific IFN-gamma-secreting T cells declined during 28 mo of follow-up with an average percentage decline of 5.8% per year (p = 0.005), while the frequencies of Ag-specific IL-2-secreting T cells increased during treatment (p = 0.02). These contrasting dynamics for the two cytokines led to a progressive convergence of the frequencies of IFN-gamma- and IL-2-secreting cells over 28 mo. Simultaneous measurement of IFN-gamma and IL-2 secretion at the single-cell level revealed a codominance of IFN-gamma-only secreting and IFN-gamma/IL-2 dual secreting CD4(+) T cells in active disease that shifted to dominance of IFN-gamma/IL-2-secreting CD4(+) T cells and newly detectable IL-2-only secreting CD4(+) T cells during and after treatment. These distinct T cell functional signatures before and after treatment suggest a novel immunological marker of mycobacterial load and clinical status in tuberculosis that now requires validation in larger prospective studies.
authors.affiliation: Tuberculosis Immunology Group, Department of Respiratory Medicine, National Heart and Lung Institute, Wright Fleming Institute of Infection and Immunity, Imperial College London, London, United Kingdom.
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Millington
authors.forename: John A
authors.initials: JA
authors.lastname: Innes
authors.forename: Sarah
authors.initials: S
authors.lastname: Hackforth
authors.forename: Timothy S C
authors.initials: TS
authors.lastname: Hinks
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Deeks
authors.forename: Davinder P S
authors.initials: DP
authors.lastname: Dosanjh
authors.forename: Valerie
authors.initials: V
authors.lastname: Guyot-Revol
authors.forename: Rubamalaar
authors.initials: R
authors.lastname: Gunatheesan
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.forename: Ajit
authors.initials: A
authors.lastname: Lalvani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007376:Interleukin-2; D007371:Interferon-gamma