| First Author | Van DV | Year | 2018 |
| Journal | Am J Respir Cell Mol Biol | Volume | 59 |
| Issue | 4 | Pages | 437-447 |
| PubMed ID | 29676593 | Mgi Jnum | J:319299 |
| Mgi Id | MGI:6863595 | Doi | 10.1165/rcmb.2017-0309OC |
| Citation | Van DV, et al. (2018) ICOS Costimulation Differentially Affects T Cells in Secondary Lymphoid Organs and Inflamed Tissues. Am J Respir Cell Mol Biol 59(4):437-447 |
| abstractText | B-cell interaction with follicular helper T cells and subsequent differentiation of B cells into high-affinity APCs 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 that allows direct comparison of immune reactions in the lung-draining lymph node and the lung tissue as well as assessment of the relative importance of dendritic cells versus B cells as APCs. 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 T-helper cell type 2 (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 ligand expression on B cells was of particular importance. Taken together, the results of this study show 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 cell responses at both sites. |
