Negative Regulation of CD4 Lineage Development and Responses by CD5

Peña-Rossi, C; Zuckerman, L; Strong, Julie; Kwan, Joanne; Ferris, William F.; Chan, Susan; Tarakhovsky, Alexander; Beyers, Albertus D.; Killeen, Nigel

doi:10.4049/jimmunol.163.12.6494

Cited by 73 publications

(2 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD5-deficient T cells are hyperresponsive to TCR stimulation, suggesting that CD5 can act as a negative regulator of TCR signaling ( 83 , 84 ). CD5 and Nur77-GFP are both surrogate markers of tonic TCR signaling ( 3 ).…”

Section: Discussionmentioning

confidence: 99%

Cbl-b mitigates the responsiveness of naive CD8 ⁺ T cells that experience extensive tonic T cell receptor signaling

Eggert,

Zinzow-Kramer,

et al. 2024

Sci. Signal.

View full text Add to dashboard Cite

Naive T cells experience tonic T cell receptor (TCR) signaling in response to self-antigens presented by major histocompatibility complex (MHC) in secondary lymphoid organs. We investigated how relatively weak or strong tonic TCR signals influence naive CD8 + T cell responses to stimulation with foreign antigens. The heterogeneous expression of Nur77-GFP, a transgenic reporter of tonic TCR signaling, in naive CD8 + T cells suggests variable intensities or durations of tonic TCR signaling. Although the expression of genes associated with acutely stimulated T cells was increased in Nur77-GFP HI cells, these cells were hyporesponsive to agonist TCR stimulation compared with Nur77-GFP LO cells. This hyporesponsiveness manifested as diminished activation marker expression and decreased secretion of IFN-γ and IL-2. The protein abundance of the ubiquitin ligase Cbl-b, a negative regulator of TCR signaling, was greater in Nur77-GFP HI cells than in Nur77-GFP LO cells, and Cbl-b deficiency partially restored the responsiveness of Nur77-GFP HI cells. Our data suggest that the cumulative effects of previously experienced tonic TCR signaling recalibrate naive CD8 + T cell responsiveness. These changes include gene expression changes and negative regulation partially dependent on Cbl-b. This cell-intrinsic negative feedback loop may enable the immune system to restrain naive CD8 + T cells with higher self-reactivity.

show abstract

Section: Discussionmentioning

confidence: 99%

Cbl-b mitigates the responsiveness of naive CD8 ⁺ T cells that experience extensive tonic T cell receptor signaling

Eggert,

Zinzow-Kramer,

et al. 2024

Sci. Signal.

View full text Add to dashboard Cite

show abstract

“…Based on studies performed primarily with murine T cells, CD5 was posited as a negative regulator of T cell function ( 27 , 28 , 60 ). However, emerging studies indicate its ability to induce T cell activation and pathogenic T H 17 cell differentiation ( 34 , 35 ).…”

Section: Discussionmentioning

confidence: 99%

CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses

Roussak

et al. 2023

Science

View full text Add to dashboard Cite

The induction of proinflammatory T cells by dendritic cell (DC) subtypes is critical for antitumor responses and effective immune checkpoint blockade (ICB) therapy. Here, we show that human CD1c + CD5 + DCs are reduced in melanoma-affected lymph nodes, with CD5 expression on DCs correlating with patient survival. Activating CD5 on DCs enhanced T cell priming and improved survival after ICB therapy. CD5 + DC numbers increased during ICB therapy, and low interleukin-6 (IL-6) concentrations promoted their de novo differentiation. Mechanistically, CD5 expression by DCs was required to generate optimally protective CD5 hi T helper and CD8 + T cells; further, deletion of CD5 from T cells dampened tumor elimination in response to ICB therapy in vivo. Thus, CD5 + DCs are an essential component of optimal ICB therapy.

show abstract

Residues Y429 and Y463 of the human CD5 are targeted by protein tyrosine kinases

et al. 2001

View full text Add to dashboard Cite

The human CD5 lymphocyte cell surface co‐receptor modulates activation and differentiation responses mediated by the antigen‐specific receptor of T and B cells. CD5 is phosphorylated followinglymphocyte activation; however, the exact sites and kinases involved are yet to be determined. Jurkat T cell transfectants expressing tyrosine‐mutated CD5 molecules have been used to show that residues Y429 and Y463 are targeted in vivo by protein tyrosine kinases following cell stimulation with anti‐CD3 mAb or pervanadate. This is in agreement with data from direct in vitrokinase assays using purified recombinant Lck and Fyn protein tyrosine kinases. The analysis of Lck‐ and CD3‐deficient Jurkat cells shows that tyrosine phosphorylation of CD5 requires Lck activity. We propose that T cell activation mediates CD5 tyrosine phosphorylation at residues Y429 and Y463 mainly through the activation of Lck.

show abstract

Negative Regulation of CD4 Lineage Development and Responses by CD5

Cited by 73 publications

References 63 publications

Cbl-b mitigates the responsiveness of naive CD8 ⁺ T cells that experience extensive tonic T cell receptor signaling

Cbl-b mitigates the responsiveness of naive CD8 ⁺ T cells that experience extensive tonic T cell receptor signaling

CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses

Residues Y429 and Y463 of the human CD5 are targeted by protein tyrosine kinases

Contact Info

Product

Resources

About

Negative Regulation of CD4 Lineage Development and Responses by CD5

Cited by 73 publications

References 63 publications

Cbl-b mitigates the responsiveness of naive CD8 + T cells that experience extensive tonic T cell receptor signaling

Cbl-b mitigates the responsiveness of naive CD8 + T cells that experience extensive tonic T cell receptor signaling

CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses

Residues Y429 and Y463 of the human CD5 are targeted by protein tyrosine kinases

Contact Info

Product

Resources

About

Cbl-b mitigates the responsiveness of naive CD8 ⁺ T cells that experience extensive tonic T cell receptor signaling

Cbl-b mitigates the responsiveness of naive CD8 ⁺ T cells that experience extensive tonic T cell receptor signaling