| Autor: |
Höhn, Hanni, Kortsik, Cornelius, Nilges, Katja, Necker, Antje, Freitag, Kirsten, Tully, Glenn, Neukirch, Claudia, Maeurer, Markus J. |
| Předmět: |
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| Zdroj: |
Immunology; Nov2001, Vol. 104 Issue 3, p278-288, 11p |
| Abstrakt: |
SummaryCD8+ T cells can be grouped into two different types of secretory T lymphocytes, based on the cytokine-secretion pattern upon antigen exposure: those with a T-cell cytotoxic type 1 response (Tc1), which secrete interferon-γ (IFN-γ), or those with a T-cell cytotoxic type 2 response, which secrete interleukin (IL)-4 and IL-10. We examined the CD8+ T-cell response directed against an immunodominant human leucocyte antigen (HLA)-A2-presented peptide derived from a 19-kDa Mycobacterium tuberculosis-associated antigen. T cells were examined by functional analysis and by T-cell receptor (TCR) complementarity-determining region 3 (CDR3)-spectratyping, which defines the complexity of a T-cell response. T-cell stimulation with the immunodominant VLTDGNPPEV epitope yielded a Tc2 (IL-4) cytokine-secretion pattern and resulted in oligoclonal expansion of TCR-variable beta chain (VB) families, which differed from patient to patient. Generation of T-cell clones corroborated the notion that the CD8+ T-cell response directed against the HLA-A2-presented VLTDGNPPEV epitope leads to a Tc2 cytokine-secretion pattern in CD8+ T cells, as defined by IL-4 and granulocyte–macrophage colony-stimulating factor (GM-CSF) release. Characterization of the cytokine-secretion profile in HLA-A2/VLTDGNPPEV-tetramer sorted T cells from patients with active tuberculosis supported this observation: peptide-specific T cells from three of three patients secreted IL-4 and only one of three patients produced IFN-γ in response to the nominal target epitope. Permutation of this T-cell epitope may aid to elicit a qualitatively different CD8+ T-cell response in patients with M. tuberculosis infection. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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