Research ArticleINFECTIOUS DISEASE

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

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Science Immunology  01 Dec 2017:
Vol. 2, Issue 18, eaam8686
DOI: 10.1126/sciimmunol.aam8686

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Clearing chronic viral infections

Although chronic lymphocytic choriomeningitis virus (LCMV) infection in mice persists for several months and is accompanied by exhaustion of CD8+ T cells, eventually the infection is controlled in most cases. Here, Greczmiel et al. have examined how these chronically infected mice clear LCMV. By developing mouse models to selectively deplete CD4+ T follicular helper cells (TFH), the authors found these TFH cells to be vital for the generation of neutralizing antiviral antibodies that promote viral clearance. The study underscores the importance of TFH cells in driving B cell responses in the context of CD8+ T cell exhaustion.

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 (TFH) lineage. Whether these TFH 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 TFH cells can be conditionally ablated, we have established that these TFH cells do in fact play an important protective function. Specifically, we demonstrate that these TFH 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 TFH cells promotes control of the chronic infection in face of exhausted CD8 T cell responses.

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