To identify new TH1-specific cell-surface proteins the authors immunized rats with TH1-cell clones and from these animals generated and screened a panel of approximately 20,000 monoclonal antibodies. Two of the antibodies recognize a cell-surface protein present on TH1 cells but absent from TH2 cells. This protein was identified as Tim-3. Further experiments showed that Tim-3 is expressed on TH1 cells but not on naïve T cells, B cells, macrophages or dendritic cells. Tim-3 is not detectable on TH1 cells until cells have undergone three rounds of polarization with TH1-inducing cytokines. Expression at this late stage of T-cell development suggests that Tim-3 might not be involved in T-cell differentiation but could be important for the effector function of TH1 cells.
Monney and co-workers next investigated the effect of Tim-3 antibody administration on the development of experimental autoimmune encephalitis (EAE), a mouse model of multiple sclerosis, which is a TH1-mediated autoimmune disease of the central nervous system. Mice susceptible to EAE were immunized with an encephalitogenic protolipid protein peptide component of myelin, given anti-Tim-3 antibody and monitored for the development of EAE. Mice treated with anti-Tim-3 antibodies rapidly developed more severe disease than control mice, showing enhanced inflammation and demyelination. The demyelinating lesions in the anti-Tim-3 antibody-treated mice were filled with activated macrophages — one of the major cell types responsible for myelin destruction in EAE — which might explain the exacerbated disease in these animals.
This is a preview of subscription content, access via your institution
