Human [CD8.sup.+] T-cells recognizing peptides from mycobacterium tuberculosis (Mtb) presented by HLA-E have an Unorthodox Th2-like, multifunctional, Mtb inhibitory phenotype and represent a novel human T-cell subset

Citation metadata

From: PLoS Pathogens(Vol. 11, Issue 3)
Publisher: Public Library of Science
Document Type: Report
Length: 10,789 words
Lexile Measure: 1590L

Document controls

Main content

Abstract :

Mycobacterial antigens are not exclusively presented to T-cells by classical HLA-class Ia and HLA-class II molecules, but also through alternative antigen presentation molecules such as CD1a/b/c, MR1 and HLA-E. We recently described mycobacterial peptides that are presented in HLA-E and recognized by CD[8.sup.+] T-cells. Using T-cell cloning, phenotyping, microbiological, functional and RNA-expression analyses, we report here that these T-cells can exert cytolytic or suppressive functions, inhibit mycobacterial growth, yet express GATA3, produce Th2 cytokines (IL-4,-5,-10,-13) and activate B-cells via IL-4. In TB patients, Mtb specific cells were detectable by peptide-HLA-E tetramers, and IL-4 and IL-13 were produced following peptide stimulation. These results identify a novel human T-cell subset with an unorthodox, multifunctional Th2 like phenotype and cytolytic or regulatory capacities, which is involved in the human immune response to mycobacteria and demonstrable in active TB patients' blood. The results challenge the current dogma that only Th1 cells are able to inhibit Mtb growth and clearly show that Th2 like cells can strongly inhibit outgrowth of Mtb from human macrophages. These insights significantly expand our understanding of the immune response in infectious disease.

Source Citation

Source Citation   

Gale Document Number: GALE|A418465313