Early lymphoid responses and germinal center formation correlate with lower viral load set points and better prognosis of simian immunodeficiency virus infection.

We have investigated the dynamics of germinal center (GC) formation in lymphoid tissues following acute SIV infection. SIV induces a marked follicular hyperplasia, associated with an aberrant accumulation of nonproliferating T follicular helper cells within GCs, but with an abundance of cells producing IL-21, demonstrating that the mechanisms involved for these two events appear independent. IL-21-stimulated T follicular helper cells are considered a critical element for GC formation, a physiological process that seems dysregulated and excessive during HIV/SIV infection, contributing to lymphoid pathogenesis. However, the data suggest that the kinetics by which such GCs are formed may be an important predictor of the host-pathogen equilibrium, as early GC hyperplasia was associated with better control of viral replication. In contrast, monkeys undergoing fast disease progression upon infection exhibited an involution of GCs without local IL-21 production in GCs. These results provide important clues regarding GC-related hyperimmune responses in the context of disease progression within various individuals during HIV/SIV infection and may open novel therapeutic avenues to limit lymphoid dysfunction, postinfection.