Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antigens, CD / analysis
-
Antigens, CD / biosynthesis
-
Antigens, Differentiation / biosynthesis
-
Antigens, Differentiation, T-Lymphocyte / analysis
-
CD4-Positive T-Lymphocytes / chemistry
-
CD4-Positive T-Lymphocytes / immunology*
-
CTLA-4 Antigen
-
Cell Proliferation*
-
Cells, Cultured
-
Forkhead Transcription Factors / analysis
-
Glucocorticoid-Induced TNFR-Related Protein
-
Humans
-
In Vitro Techniques
-
Interferon-gamma / biosynthesis
-
Interleukin-2 Receptor alpha Subunit / analysis
-
Interleukin-7 Receptor alpha Subunit / analysis
-
Lectins, C-Type
-
Leukocytes, Mononuclear
-
Mycobacterium bovis / immunology
-
Receptors, Nerve Growth Factor / biosynthesis
-
Receptors, OX40 / biosynthesis
-
Receptors, Tumor Necrosis Factor / biosynthesis
-
T-Lymphocyte Subsets / immunology*
-
T-Lymphocytes, Regulatory / chemistry
-
T-Lymphocytes, Regulatory / immunology*
-
Transforming Growth Factor beta / immunology
-
Tuberculosis / immunology*
Substances
-
Antigens, CD
-
Antigens, Differentiation
-
Antigens, Differentiation, T-Lymphocyte
-
CD69 antigen
-
CTLA-4 Antigen
-
CTLA4 protein, human
-
FOXP3 protein, human
-
Forkhead Transcription Factors
-
Glucocorticoid-Induced TNFR-Related Protein
-
Interleukin-2 Receptor alpha Subunit
-
Interleukin-7 Receptor alpha Subunit
-
Lectins, C-Type
-
Receptors, Nerve Growth Factor
-
Receptors, OX40
-
Receptors, Tumor Necrosis Factor
-
TNFRSF18 protein, human
-
TNFRSF4 protein, human
-
Transforming Growth Factor beta
-
Interferon-gamma