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Thymic stromal lymphopoietin limits primary and recall CD8+ T cell anti-viral responses

ABSTRACT: Thymic stromal lymphopoietin (TSLP) is a cytokine that acts directly on CD4+ T cells and dendritic cells to promote progression of asthma, atopic dermatitis, and allergic inflammation. However, a direct role for TSLP in CD8+ T-cell primary responses remains controversial and its role in memory CD8+ T-cell responses to secondary viral infection is unknown. Here, we investigate the role of TSLP in both primary and recall responses using two different viral systems. Interestingly, TSLP limited the primary CD8+ T cell response to influenza but did not affect T cell function nor significantly alter the number of memory CD8+ T cells generated after influenza infection. However, TSLP inhibited memory CD8+ T cell responses to secondary viral infection with influenza or acute systemic LCMV infection. These data reveal a previously unappreciated role for TSLP on recall CD8+ T cell responses in response to viral infection, findings with potential translational implications.

ORGANISM(S): Mus musculus

PROVIDER: GSE156875 | GEO | 2021/01/05

REPOSITORIES: GEO

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The PD-1 pathway regulates development and function of memory CD8+ T cells following respiratory viral infection

Project description:The PD-1:PD-L co-inhibitory pathway regulates dysfunctional T cells in chronic viral infection and cancer, but the role of this pathway in effector and memory responses following acute infection or vaccination remains less clear. Here we demonstrated that in the absence of signals from the PD-1 pathway, cell intrinsic alterations during initial CD8+ T cell priming resulted in excessive early CD8+ T cell expansion, but increased CD8+ T cell contraction and aberrant effector to memory CD8+ T cell transition. Overall, our studies revealed a critical and previously unappreciated role for PD-1 as an integrator of early CD8+ T cell activation signals that promoted optimal CD8+ T cell memory formation and durability. This novel PD-1 function has therapeutic implications for the generation of T cell memory during PD-1 cancer immunotherapy and modulation of the PD-1 pathway to enhance immune memory following acute infection or prophylactic vaccination. Microarrays were performed on influenza-specific CD8+ T cells isolated from the lungs of wildtype and PD-L1/L2 double knockout mice that were infected intranasally with X31-GP33. Influenza-specific CD8+ T cells were harvested at day 8 in order to determine the global program of gene expression at during the effector phase of the response to influenza to begin to dissect the role of PD-1 signaling early during effector and memory differentiation.

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2023-01-30 | E-MTAB-11116 | biostudies-arrayexpress

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