ICOS Costimulation Differentially Affects T Cells in Secondary Lymphoid Organs and Inflamed Tissues.

B cell interaction with follicular helper T cells and their subsequent differentiation into high-affinity antibody producing cells normally takes place in secondary lymphoid organs. The costimulator ICOS plays a key role in this process and is therefore considered as an attractive target to modulate exaggerated B cell responses in autoimmune or allergic diseases. Inflamed tissues were recently recognized as additional sites of active T cell/B cell interaction. To analyze whether ICOS costimulation is also important there, we employed a mouse airway inflammation model which allows to directly compare immune reactions in the lung-draining lymph node and the lung tissue and also to assess the relative importance of dendritic cells versus B cells as antigen-presenting cells. In both organs ICOS regulated the pool size of antigen-specific T and B cells and B cell-differentiation into germinal center (-like) cells but not into antibody-secreting cells. In the lymph node, lack of ICOS costimulation drastically reduced the frequency of T follicular helper cells but did not affect production of Th2 cytokines. Vice versa in the lung tissue, ICOS did not change PD-1 expression on infiltrating T cells but regulated Th2 cytokine production, a process for which ICOS-L expression on B cells was of particular importance. Taken together, this study shows that ICOS differentially regulates effector T cells in secondary lymphoid organs and inflamed tissues but that blockade of the ICOS pathway is suitable to target T cell-dependent B cells responses at both sites.