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Murine γδ T cells participate in the innate immune response against infection by an intracellular pathogen Listeria monocytogenes. Vδ1+γδ T cells coexpressing Vγ6 are a major γδ T-cell subpopulation induced at an early stage of L. monocytogenes infection in the livers of infected mice. To investigate the protective role of the Vγ6/Vδ1+γδ T cells against L. monocytogenes infection, Vδ1 gene-deficient (Vδ1−/−) mice were analysed because these mice selectively lacked a Vγ6/Vδ1+γδ T-cell subpopulation in the L. monocytogenes-infected liver. The Vδ1−/− mice showed increased bacterial burden in the liver and spleen, and decreased survival rate at an early stage of L. monocytogenes infection when compared to wild-type mice. Histological examination showed abscess-like lesions and unorganized distribution of macrophages in the liver of the Vδ1−/− mice but not in the wild-type mice after L. monocytogenes infection. The Vγ6/Vδ1+γδ T cells produced interferon-γ and interleukin-17A. All the results suggest that murine Vγ6/Vδ1+γδ T cells control the innate protective response against L. monocytogenes infection through production of the proinflammatory cytokines interferon-γ and interleukin-17A in the infected liver. [ABSTRACT FROM AUTHOR]

Summary The Fas/Fas ligand (FasL) system plays important roles in the immune system, including host immunoregulation and cytotoxicity. In this study, we investigated the involvement of Fas–FasL interactions in spontaneous acceptance of hepatic allografts in murine orthotopic liver transplantation. Liver transplantation between the C57BL/6 (B6, H-2b ) donor and the MRL/Mp (MRL, H-2k ) recipient was performed in various combinations of donor and recipient mice with wild type (+/+), Fas-mutant (lpr ) or FasL-mutant (gld ) genotypes. The prolongation and spontaneous acceptance of the fully allogeneic grafts in recipients was not observed in either MRL-lpr recipients with B6+/+ livers or MRL+/+ recipients with B6-gld livers. Moreover, the serum alanine aminotransferase (ALT) levels and the degree of cell infiltration into hepatic allografts on day 7 after transplantation were inversely correlated with the recipient survival time (in days). The donor-specific cytotoxic T-lymphocyte (CTL) activities of the graft-infiltrating cells (GICs) from MRL-gld recipients with B6+/+ livers were much lower than those from MRL+/+ or -lpr recipients on days 5 and 10 after transplantation. However, the CTL activities of the GICs from MRL+/+ and -gld recipients predominately disappeared by day 15 after transplantation. Furthermore, the anti-donor CTL activities induced in MRL+/+ recipients were ascribed to CD8+ cells, and were not mediated by Fas–FasL interactions. These results strongly suggest that the Fas/FasL system plays a critical role for recipient immunoregulation, enabling recipients in accepting hepatic allografts by deletion of the donor-specific T cells, but not for CTL/target cell interaction in MRL+/+ recipients. [ABSTRACT FROM AUTHOR]

Objective: To determine whether eyedrop administration of an anti-CD4 monoclonal antibody (mAb) is effective in the treatment of Sjögren's syndrome (SS) using a mouse model of the disease., Methods: The anti-CD4 mAb was administered daily into the eyes of mice with SS from ages 4 to 8 weeks or ages 10 to 12 weeks. During treatment, tear volume was monitored and after final treatment, histologic features of the lacrimal and salivary glands, the phenotypes and function of T cells, and serum titers of anti-alpha-fodrin antibody were examined., Results: Eyedrop administration of anti-CD4 mAb before the onset of SS prevented the autoimmune pathology seen in the lacrimal glands but not that in the salivary glands. Furthermore, eyedrop administration of anti-CD4 mAb after the development of SS inhibited mononuclear cell infiltration and the destruction of parenchyma only in the lacrimal glands. Eyedrop administration of anti-CD4 mAb suppressed the local activation of CD4+ T cells rather than deleting CD4+ T cells, which reduced the expansion of pathologic CD4+ T cells against alpha-fodrin., Conclusion: These results demonstrate the remarkable efficacy of anti-CD4 mAb eyedrops in the treatment of SS eye symptoms, which illustrates a new antibody-based therapeutic strategy for patients with eye problems caused by SS as well as other diseases.