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Direct upregulation of human CD4+ T cell proliferation and cytokine secretion by Mycobacterium tuberculosis (MTB)
Author(s) -
Lancioni Christina Louise,
Thomas Jeremy,
Ding Xuedong,
Pecora Nicole D.,
Drage Michael,
Harding Clifford,
Boom W. Henry,
Rojas Roxana E.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.860.4
Subject(s) - cd28 , t cell , cell sorting , microbiology and biotechnology , antigen , secretion , cd3 , cd80 , biology , chemistry , mycobacterium tuberculosis , flow cytometry , cd40 , in vitro , immunology , cytotoxic t cell , immune system , biochemistry , cd8 , tuberculosis , medicine , pathology
Apart from modulating antigen presenting cell functions, recent studies suggest that MTB can directly regulate CD4+ T cell function. The current study investigates the regulatory role of MTB molecule(s) on CD4+ T cell activation in the absence of antigen presenting cells. Highly pure (99.8%) CD4+ T cells were obtained from peripheral blood of healthy PPD‐ negative donors by negative selection with mAb coated‐ magnetic beads followed by flow sorting. MTB (H37Ra) lysate was extracted with Triton X‐114; hydrophobic material was separated by SDS‐PAGE and electroelution (MTB fractions). CD4+ T cells were stimulated with suboptimal concentrations of plate‐bound anti‐CD3 plus soluble anti‐CD28 mAbs or fibronectin +/− different MTB fractions. Significant increases in CD4+ T‐cell proliferation, IL‐2‐ and IFN‐gamma secretion in response to anti‐CD3/anti‐CD28 were observed in presence of MTB fractions containing low‐molecular weight bands (<20 kDa). Up‐regulation of proliferation and IFN‐gamma was also observed in presence of MTB fractions upon stimulation with anti‐CD3 plus fibronectin. MTB fractions did not induce T cell activation when incubated in absence of TCR stimulation and a second co‐stimulatory signal (anti‐CD28 or fibronectin). Thus hydrophobic MTB fractions have a direct co‐stimulatory effect on CD4+ T cells suggesting a role of MTB in direct regulation of T cell activation.