HIV infection dramatically changes the lymph node (LN) tissue architecture and the dynamics of tissue resident immune cells, potentially affecting the ability of HIV infected individuals to respond to subsequent antigenic challenge. The dynamics of circulating and LN-resident CD4 T cell and B cell populations in cART HIV patients after trivalent seasonal influenza immunization were assessed.
LN-derived cells and PBMCs from healthy controls and virologically suppressed HIV+ patients were obtained pre- and post- vaccination and analyzed using multiparametric flow cytometry assays and multiplexed confocal imaging. Fluidigm gene expression analysis was performed to assess the effect of vaccination on the transcriptional profile of follicular CD4 T cells. Actively transcribed virus in sorted LN-cells was analysed by PCR assays.
Pre-vaccination frequencies of follicular CD4 T helper cell (TFH) between healthy donors and cART HIV+ patients at steady state were collectively similar but were highest in those with the greatest increase in antibody titers post-vaccination. This profile was also reflected at tissue level when relevant populations were investigated with imaging assays. There was a trend for lower TFH frequencies post-vaccination in HIV+ compared to HIV- individuals while B cell frequencies remained the same post-vaccination both in LN and PBMC. The transcriptional profile of TFH revealed differentially expressed genes (DEGs) between HIV- and cART treated donors. Furthermore, our transcriptional analysis revealed that vaccination had a greater impact on TFH compared to non-TFH CD4 T cells. In line with the lower frequencies of TFH, actively transcribed virus in the TFH compartment was reduced after vaccination.
Vaccination predominantly alters the frequency and phenotype of follicular CD4 T-cells in the draining LN of HIV infected patients on cART in a manner consistent with the development of IgG antibody titers. The underlying mechanism of follicular CD4 T cell mobilization warrants further investigation as it could bear implications for the rational design of HIV vaccines.