However, the precise role of LFA-1 in the pathogenesis of EAE has so far remained unclear. We describe here the disease development in LFA-1−/− mice compared with WT controls. Ablation of LFA-1 resulted in more severe EAE with increased demyelination and increased numbers of myelin oligodendrocyte glycoprotein-reactive CD4+ T cells in the CNS. However,

the production of the Pexidartinib cost pro-inflammatory cytokines IL-17 and IFN-γ was unchanged on the level of antigen-specific T cells. Interestingly, LFA-1-deficient mice showed a clearly reduced frequency of Treg in the inflamed CNS. Moreover, Treg counts in spleens and thymi of unimmunized LFA-1−/− mice were lower in comparison to the WT controls, indicating an impairment of Treg generation. In combination,

these results suggest a substantial role of LFA-1 in Treg generation and subsequent expansion of effector T cells and highlight the importance of Treg in limiting EAE. EAE is a T-cell-mediated inflammatory disease of the CNS and serves as an animal model for multiple sclerosis. The autoimmune phenotype can be induced in rodents sensitized to proteins such as myelin basic protein or myelin oligodendrocyte glycoprotein (MOG). The disease is initiated by infiltration of peripheral lymphocytes and macrophages into the CNS and is characterized by local selleck products inflammation and demyelination. The migration of leukocytes into the CNS is facilitated by interactions of cell-surface adhesion molecules and their endothelial ligands 1. The family of β2-integrins is involved in leukocyte–vascular cell interactions as well as in the communication between T cells and antigen-presenting cells. The αLβ2-integrin LFA-1 (CD11a/CD18) is widely expressed by leukocytes including peripheral blood lymphocytes, monocytes, and NK cells 2. Among the members of CYTH4 the β2 family of integrins, only LFA-1 is expressed by CD4+ T cells and CD4+ CD25+ Treg 3. Interestingly, CD18-deficient mice, which do not express

β2-integrins, showed an impaired development of thymic and peripheral Treg, but it remained unclear which of the β2-integrins is responsible for this phenotype 3. The function of LFA-1 in EAE has been extensively studied. However, in part controversial and conflicting results have been obtained. For example, treatment with anti-LFA-1 Ab led to either protection against EAE 4 or more severe disease development 5. More recently, a deficiency for LFA-1 was suggested to dampen EAE upon active induction of an autoimmune response 6. On the other hand, adoptive transfer of WT encephalitogenic T cells into LFA-1−/− mice profoundly exacerbated the EAE course in comparison to WT mice, indicating an anti-inflammatory role of LFA-1, which would limit disease progression 7. It remained, however, elusive how LFA-1 exerts its immunosuppressive effects.