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The adaptor molecule CD2AP in CD4 T cells modulates differentiation of follicular
helper T cells during chronic LCMV infection
#MMPMID29734372
Raju S
; Kometani K
; Kurosaki T
; Shaw AS
; Egawa T
PLoS Pathog
2018[May]; 14
(5
): e1007053
PMID29734372
show ga
CD4 T cell-mediated help to CD8 T cells and B cells is a critical arm of the
adaptive immune system required for control of pathogen infection. CD4 T cells
express cytokines and co-stimulatory molecules that support a sustained CD8 T
cell response and also enhance generation of protective antibody by germinal
center B cells. However, the molecular components that modulate CD4 T cell
functions in response to viral infection or vaccine are incompletely understood.
Here we demonstrate that inactivation of the signaling adaptor CD2-associated
protein (CD2AP) promotes CD4 T cell differentiation towards the follicular helper
lineage, leading to enhanced control of viral infection by augmented germinal
center response in chronic lymphocytic choriomeningitis virus (LCMV) infection.
The enhanced follicular helper differentiation is associated with extended
duration of TCR signaling and enhanced cytokine production of CD2AP-deficient CD4
T cells specifically under TH1 conditions, while neither prolonged TCR signaling
nor enhanced follicular helper differentiation was observed under conditions that
induce other helper effector subsets. Despite the structural similarity between
CD2AP and the closely related adaptor protein CIN85, we observed defective
antibody-mediated control of chronic LCMV infection in mice lacking CIN85 in T
cells, suggesting non-overlapping and potentially antagonistic roles for CD2AP
and CIN85. These results suggest that tuning of TCR signaling by targeting CD2AP
improves protective antibody responses in viral infection.
|Adaptor Proteins, Signal Transducing/immunology/*metabolism/physiology
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