The aged microenvironment impairs BCL6 and CD40L induction in CD4+ T follicular helper cell differentiation 2437

Abstract Description Weakened germinal center responses by the aged immune system result in diminished immunity against pathogens and reduced efficacy of vaccines. Prolonged contacts between activated B cells and CD4+ T cells are crucial to germinal center formation and Tfh differentiation, but it is unclear how aging impacts the quality of this interaction. Peptide immunization confirmed that aged mice have decreased expansion of antigen-specific GC B cells and reduced antibody titers. Aging was associated with accumulated Tfh cells with reduced BCL6 and increased CD39. When activated in vitro by aged antigen-presenting cells, young CD4+ naïve T cells generated reduced numbers of activated cells with upregulated CD40L. To determine the contribution of cell-extrinsic influences on antigen-specific Tfh induction, young, antigen-specific B and CD4+ T cells were transferred into aged hosts prior to immunization. Transferred cells had reduced expansion and differentiation into germinal center B cell and Tfh and reduced antigen-specific antibody titers when compared to young hosts. Young CD4+ T cells transferred into aged hosts differentiated into Tfh cells with reduced PD-1 and BCL6, and increased CD39. Recent studies have focused on immune profiling of CD4 T cells in young and aged mice following immunization. These results highlight the role of the lymphoid microenvironment in modulating CD4+ T cell differentiation, which contributes to impaired initiation and maintenance of germinal centers. Funding Sources Research was supported by NIH/NIA R01 AG080037 and the Mayo Clinic Robert and Arlene Kogod Center on Aging Innovation Award UL1R002377 to J.L. Topic Categories Vaccines and Immunotherapy (VAC)