In vitro expansion of CD4+CD25highFOXP3+CD127low/- regulatory T cells from peripheral blood lymphocytes of healthy Mycobacterium tuberculosis-infected humans.
CD4+CD25highFOXP3+ regulatory T (Treg) cells have recently been found at elevated levels in the peripheral blood of tuberculosis patients, compared to Mycobacterium tuberculosis latently infected (LTBI) healthy individuals and non-infected controls. Here, we show that CD4+CD25highFOXP3+ T lymphocytes can be expanded in vitro from peripheral blood mononuclear cells (PBMC) of LTBI individuals, but not of uninfected controls by incubating them with BCG in the presence of TGF-beta. These expanded cells from the PBMC of LTBI subjects expressed CTLA-4, GITR and OX-40, but were CD127low/- and have therefore the phenotype of Treg cells. In addition, they inhibited in a dose-dependant manner the proliferation of freshly isolated mononuclear cells in response to polyclonal stimulation, indicating that they are functional Treg lymphocytes. In contrast, incubation of the PBMC with BCG alone preferentially induced activated CD4+ T cells, expressing CD25 and/or CD69 and secreting IFN-gamma. These results show that CD4+CD25highFOXP3+ Treg cells can be expanded or induced in the peripheral blood of LTBI individuals in conditions known to predispose to progression towards active tuberculosis and may therefore play an important role in the pathogenesis of the disease.
Hougardy
Jean-Michel
JM
Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles, Belgium.
Verscheure
Virginie
V
Locht
Camille
C
Mascart
Françoise
F
D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D060908:CTLA-4 Antigen; D049109:Cell Proliferation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000032:analysis; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear; D009163:Mycobacterium bovis / Q000276:immunology; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis; D053262:Receptors, OX40 / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D060908:CTLA-4 Antigen; D051858:Forkhead Transcription Factors; D053450:Glucocorticoid-Induced TNFR-Related Protein; D007371:Interferon-gamma; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D037181:Lectins, C-Type; D017475:Receptors, Nerve Growth Factor; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D016212:Transforming Growth Factor beta; D000099192:CD69 Antigens; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; C491405:TNFRSF18 protein, human; C505716:TNFRSF4 protein, human