Sustained T follicular helper cell response is essential for control of chronic viral infection

Abstract

During chronic viral infections, both CD8 and CD4 T cell responses are functionally compromised. Alongside exhaustion of CD8 T cells during chronic viral infections, it has also been documented that the CD4 T cells have an increased propensity to differentiate toward CXCR5⁺ T follicular helper cell (T_FH) lineage. Whether these T_FH cells contribute to the immune response to chronic viral infection has remained unclear. Using chronic lymphocytic choriomeningitis virus (LCMV) infection in conjunction with an in vivo system where T_FH cells can be conditionally ablated, we have established that these T_FH cells do in fact play an important protective function. Specifically, we demonstrate that these T_FH cells are essential for the late emergence of neutralizing LCMV-specific antibodies that keep viral titers in check and ultimately allow mice to clear the virus. By supporting the generation of neutralizing antibodies, we show that sustained activity of T_FH cells promotes control of the chronic infection in face of exhausted CD8 T cell responses.