Figure 2.

Reduced vaccine response in the elderly. Upon antigenic stimulation, antigen presenting cells capture, process and present the antigen to naïve CD4⁺ T cells in the draining lymph node. Upon the formation of an immunological synapse between these two cell types, in young individuals naïve CD4⁺ T cells get efficiently activated and acquire a T_FH-like phenotype by up-regulating Bcl-6, ICOS, SLAMFF6 and GL-7. Consequently, they migrate to the GC, where they will sustain a T cell-depedent B-cell response. Finally, mature plasma cells will be generated, and they will produce high-affinity antibodies against the antigen, thereby providing a good vaccine response. In contrast, in older individuals typically a scares response to vaccines is observed. Among the possible causes, it was found that activated CD4⁺ T cells failed to up-regulate some T_FH cell markers, which are crucial to promote migration towards the GC, thus a reduced amount of T cells reach this location. Moreover, upon antigenic stimulation, a higher frequency of T_FR cells can be found in the GC, which inevitably results in the suppression of this T cell-dependent B cell responses.