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

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. Overall design: RNA-Seq analysis on sorted naïve and memory CD8+ T cells after 4 or 24 hours incubation with medium or TSLP with or without TCR stimulation. RNA-Seq analysis on recall responses of wild-type and Tslpr-/- CD8+ T cells at day 8 after secondary infection.