Reduced T follicular helper function in aged mice is correlated with increased numbers of T regulatory cells (LYM2P.725)

Abstract

Abstract T follicular helper (TFH) cells are critical for a germinal center response and a robust humoral response. Aging has a profound impact on the formation of a strong humoral/germinal center response, yet the impact of aging on TFH remains unclear. This study explores the effects of aging on TFH transcription factors, which could explain some of the age related germinal center defects. During influenza infection, young mice exhibit a very robust IgG response, which is significantly reduced in aged mice. Initial studies showed that there are no differences in the number of flu-specific TFH (CXCR5hi PD-1hi) during the course of the infection, as determined using MHC class II NP tetramer. To determine transcription factor expression and localization of TFH, we performed multicolor flow cytometry and confocal microscopy on spleens from these mice. There was no difference in BCL6 expression in young and aged flu-specific TFH. But, strikingly, flu-specific BCL6hi TFH from aged mice had increased co-expression of Foxp3, characteristic of T follicular regulatory cells, a critical controller of germinal center responses. We are currently exploring the contribution of whether the differences in TFH transcription factor expression are intrinsic to aged CD4+ T cells or are a result of the aged microenvironment. These results strongly suggest that aging has a dramatic impact on transcription factor expression in CD4 T cells, which can influence the establishment of a robust immune response.