Lymphoid reservoirs of antigen-specific memory T helper cells

How vaccines control the development of antigen-specific effector and memory T helper cells is central to protective immunity but remains poorly understood. Here we found that protein vaccination selected high-affinity, CXCR5(+)ICOS(hi) follicular B-helper T cells (T-FH cells) that developed in draining lymphoid tissue to regulate B cell responses. In the memory phase, reservoirs of antigen-specific CXCR5(+)ICOS(lo) T-FH cells persisted with less effector activity but accelerated antigen-recall ability. This new compartment of memory T-FH cells was retained in draining lymphoid sites with antigen-specific memory B cells, persistent complexes of peptide and major histocompatibility complex class II and continued expression of CD69. Thus, protein vaccination promotes B cell immunity by selecting high-affinity effector T-FH cells and creating lymphoid reservoirs of antigen-specific memory T-FH cells in vivo.