title: Circulating, Mycobacterium tuberculosis-specific lymphocytes from PPD skin test-negative patients with tuberculosis do not secrete interferon-gamma (IFN-gamma) and lack the cutaneous lymphocyte antigen skin-selective homing receptor.
abstract: Individuals with a negative intradermal reaction to tuberculin PPD have long been described in the Mycobacterium tuberculosis exposed, immune-competent population. Here, we studied PPD-specific blood T lymphocytes from these subjects for phenotypic markers relevant to skin migration, including the expression of the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen (CLA). Out of 82 patients with active tuberculosis we identified four subjects who were repeatedly PPD skin test-negative. CD4 T lymphocytes specific to mycobacterial antigens were derived from these individuals, which (i) proliferated in vitro to M. tuberculosis antigens comparably to those from PPD+ patients; (ii) secreted comparable amounts of IL-2 but lower amounts of IFN-gamma; (iii) were confined within the CLA-negative T cell subset. We conclude that the negative tuberculin reaction in a small subset of patients exposed to mycobacteria is associated with impaired production of IFN-gamma by circulating PPD-specific T cells that are lacking CLA expression. On this basis in vitro proliferation to PPD can discriminate bona fide non-responders from infected patients with a deficit in the margination of M. tuberculosis-specific T lymphocytes.
authors.affiliation: San Raffaele Scientific Institute, the Institute Villa Marelli for Lung Diseases, Milan, Italy.
authors.forename: Z I
authors.initials: ZI
authors.lastname: Magnani
authors.forename: C
authors.initials: C
authors.lastname: Confetti
authors.forename: G
authors.initials: G
authors.lastname: Besozzi
authors.forename: L R
authors.initials: LR
authors.lastname: Codecasa
authors.forename: P
authors.initials: P
authors.lastname: Panina-Bordignon
authors.forename: R
authors.initials: R
authors.lastname: Lang
authors.forename: G A
authors.initials: GA
authors.lastname: Rossi
authors.forename: R
authors.initials: R
authors.lastname: Pardi
authors.forename: S E
authors.initials: SE
authors.lastname: Burastero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing / Q000172:deficiency*; D012867:Skin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis / Q000276:immunology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D008562:Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing; D007371:Interferon-gamma