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Human CD8 T-cells Recognizing Peptides from () Presented by HLA-E Have an Unorthodox Th2-like, Multifunctional, Inhibitory Phenotype and Represent a Novel Human T-cell Subset


Pathogens like Mycobacterium tuberculosis (Mtb) are recognized by human T-cells following their presentation in HLA molecules. HLA class I molecules can be divided into two types, classical as well as non-classical HLA molecules. Here we studied the non-classical HLA family member, HLA-E, which displays only minimal genetic variation between individuals and is relative resistant to down modulation by HIV infection. We have characterized the T-cells that recognize Mtb in the context of HLA-E in detail and found that these human CD8+ T-cells had unexpected, unorthodox properties: in contrast to most classical CD8+ T-cells, the T-cells activated by HLA-E uniquely produced Th2 (IL-4, IL-5, IL-13) instead of the usual Th1 cytokines, and were able to activate B-cells and induced cytokine production by these B-cells. Moreover, these HLA-E restricted CD8+ T-cells inhibited Mtb growth inside cells, an important property to contribute to resolution of the infection. Thus these T-cells represent a new player in the human immune response to infection, and add B-cell activation to the key pathways following infection with Mtb.


Vyšlo v časopise: Human CD8 T-cells Recognizing Peptides from () Presented by HLA-E Have an Unorthodox Th2-like, Multifunctional, Inhibitory Phenotype and Represent a Novel Human T-cell Subset. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004671
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004671

Souhrn

Pathogens like Mycobacterium tuberculosis (Mtb) are recognized by human T-cells following their presentation in HLA molecules. HLA class I molecules can be divided into two types, classical as well as non-classical HLA molecules. Here we studied the non-classical HLA family member, HLA-E, which displays only minimal genetic variation between individuals and is relative resistant to down modulation by HIV infection. We have characterized the T-cells that recognize Mtb in the context of HLA-E in detail and found that these human CD8+ T-cells had unexpected, unorthodox properties: in contrast to most classical CD8+ T-cells, the T-cells activated by HLA-E uniquely produced Th2 (IL-4, IL-5, IL-13) instead of the usual Th1 cytokines, and were able to activate B-cells and induced cytokine production by these B-cells. Moreover, these HLA-E restricted CD8+ T-cells inhibited Mtb growth inside cells, an important property to contribute to resolution of the infection. Thus these T-cells represent a new player in the human immune response to infection, and add B-cell activation to the key pathways following infection with Mtb.


Zdroje

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