| Members of the beta2-integrin family of adhesion molecules, CD11a, CD11b, and CD11c, have all been shown to play a role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). CD11d had yet to be studied in demyelinating disease and its functions remained unclear. We report here that CD11d is the only member of the beta2 -integrin family of adhesion molecules that fails to protect against the development of EAE. Surprisingly, the EAE studies suggested that CD11a, CD11b, and CD11c were all contributing to T cell activity during disease development by mechanisms beyond the migration of these cells into the CNS. However, the contributions of individual T cell subsets to the overall phenotypes seen were unclear. Earlier studies show that over the course of EAE a higher proportion of gammadelta T cells express the beta2-integrins when compared to gammadelta T cells. Given this we hypothesized that the beta 2-integrin family was important to the functions of gammadelta T cells that contributed to the development of EAE. However, we show here that even though expression is enriched in this T cell subset the beta2 -integrins do not seem to be required on gammadelta T cells for disease development. The beta2-integrin family has also been implicated in regulatory T cell function and homeostasis. Studies using transfer EAE with CD11a-/- mice have suggested these mice may have regulatory defects. Given this we next investigated the role CD11a plays in regulatory T cell biology. We show here that CD11a-/- mice have reduced Treg populations throughout the secondary lymph tissue and that this reduction may be due to a reduced capacity to generate peripheral Tregs. We also found that CD11a is critical to Treg function in vitro, but does not seem to be as important in vivo. Importantly CD11a appears to be mediating its immunosuppressive effects independently of interactions with ICAM-1 on target T cells. Overall, the studies presented here provide further evidence that the beta2-integrin family of adhesion molecules functions in many aspects of T cell biology aside from cellular migration and that these functions differ between T cell subsets. |
