Viral persistence redirects CD4 T cell differentiation toward T follicular helper cells

LM Fahey, EB Wilson, H Elsaesser… - Journal of Experimental …, 2011 - rupress.org
LM Fahey, EB Wilson, H Elsaesser, CD Fistonich, DB McGavern, DG Brooks
Journal of Experimental Medicine, 2011rupress.org
CD4 T cell responses are crucial to prevent and control viral infection; however, virus-
specific CD4 T cell activity is considered to be rapidly lost during many persistent viral
infections. This is largely caused by the fact that during viral persistence CD4 T cells do not
produce the classical Th1 cytokines associated with control of acute viral infections.
Considering that CD4 T cell help is critical for both CD8 T cell and B cell functions, it is
unclear how CD4 T cells can lose responsiveness but continue to sustain long-term control …
CD4 T cell responses are crucial to prevent and control viral infection; however, virus-specific CD4 T cell activity is considered to be rapidly lost during many persistent viral infections. This is largely caused by the fact that during viral persistence CD4 T cells do not produce the classical Th1 cytokines associated with control of acute viral infections. Considering that CD4 T cell help is critical for both CD8 T cell and B cell functions, it is unclear how CD4 T cells can lose responsiveness but continue to sustain long-term control of persistent viral replication. We now demonstrate that CD4 T cell function is not extinguished as a result of viral persistence. Instead, viral persistence and prolonged T cell receptor stimulation progressively redirects CD4 T cell development away from the Th1 response induced during an acute infection toward T follicular helper cells. Importantly, this sustained CD4 T cell functionality is critical to maintain immunity and ultimately aid in the control of persistent viral infection.
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