Oral Presentation MIN Spring Retreat 2023

B cells orchestrate early CD8 T cell priming in response to chronic viral infections (#10)

Catarina Gago da Graca 1 , Leonie Heyden 1 2 , Tommy Chung 1 , Amania Sheikh 1 , Hanh Thi Nguyen 1 , Carlson Tsui 1 , Zeinab Abdullah 2 , Axel Kallies 1 , Daniel Utzschneider 1
  1. Department of Microbiology and Immunology , The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria , Australia
  2. Institute for Experimental Immunology, University Hospital of Bonn, Rheinische Friedrich, Wilhelm University, Bonn, Germany

Following antigen encounter, naive CD8 T cells undergo rapid expansion and differentiation, including the acquisition of effector function to provide protection against pathogens. Yet, how early T cell activation is regulated by other immune cells and specific environmental cues remains incompletely understood. Here, by taking advantage of different Lymphocytic Choriomeningitis Virus (LCVM) infections, we identify a critical role for B cells in regulating early CD8 T cell response to chronic but not to acute infections. In the absence of B cells, CD8 T cells were unable to optimally accumulate and acquire effector function as evidenced by their ability to produce IFNg and TNF. Mechanistically, B cells provided key costimulatory signals and cytokines that promoted the expression of ICOS on CD8 T cells. Indeed, therapeutic inhibition of ICOS signalling in wild-type mice recapitulated the impaired T cell expansion in the absence of B cells. Our data identify a therapeutic role for costimulatory receptors in modulating T cell responses to chronic infection. Overall, we unravel the complexity of the early adaptive immune response and identify a critical role for B cells in promoting optimal CD8 T cell responses.