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CD4 and CD8 co-receptors modulate functional avidity of CD1b-restricted T cells.

ABSTRACT: T cells recognize mycobacterial glycolipid (mycolipid) antigens presented by CD1b molecules, but the role of CD4 and CD8 co-receptors in mycolipid recognition is unknown. Here we show CD1b-mycolipid tetramers reveal a hierarchy in which circulating T cells expressing CD4 or CD8 co-receptor stain with a higher tetramer mean fluorescence intensity than CD4-CD8- T cells. CD4+ primary T cells transduced with mycolipid-specific T cell receptors bind CD1b-mycolipid tetramer with a higher fluorescence intensity than CD8+ primary T cells. The presence of either CD4 or CD8 also decreases the threshold for interferon-γ secretion. Co-receptor expression increases surface expression of CD3ε, suggesting a mechanism for increased tetramer binding and activation. Targeted transcriptional profiling of mycolipid-specific T cells from individuals with active tuberculosis reveals canonical markers associated with cytotoxicity among CD8+ compared to CD4+ T cells. Thus, expression of co-receptors modulates T cell receptor avidity for mycobacterial lipids, leading to in vivo functional diversity during tuberculosis disease.

SUBMITTER: James CA

PROVIDER: S-EPMC8748927 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Human MHC Class I-restricted high avidity CD4<sup>+</sup> T cells generated by co-transfer of TCR and CD8 mediate efficient tumor rejection in vivo.

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| S-EPMC3583927 | biostudies-literature

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| S-EPMC7687044 | biostudies-literature

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| S-EPMC3014941 | biostudies-literature

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| S-EPMC3701695 | biostudies-literature

FoxP3? regulatory CD4 T cells control the generation of functional CD8 memory.

Project description:During the primary immune response, CD8 memory emerges from an environment of strong immune activation. The FoxP3(+) regulatory CD4 T-cell subset (Treg) is known as a key suppressive component of the immune system. Here we report that Tregs are required for the generation of functional CD8 memory. In the absence of Tregs during priming, the resulting memory cells proliferate poorly and fail to differentiate into functional cytotoxic secondary effectors following antigen reactivation. We find that the Tregs act early, during the expansion phase of primary CD8 effectors, by fine tuning interleukin-2 exposure of CD8 memory precursors. This crucial new role of Tregs has implications for optimal vaccine development.

| S-EPMC3432473 | biostudies-other

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