Anti-IL5 monoclonal antibody, clone TRFK5

CD4(+) T helper 2 (T(H)2) cells secrete interleukin (IL)4, IL5 and IL13, and are required for immunity to gastrointestinal helminth infections(1). However, T(H)2 cells also promote chronic inflammation associated with asthma and allergic disorders(2). The nonhaematopoietic-cell-derived cytokines thymic stromal lymphopoietin, IL33 and IL25 (also known as IL17E) have been implicated in inducing T(H)2 cell-dependent inflammation at mucosal sites(3-6), but how these cytokines influence innate immune responses remains poorly defined. Here we show that IL25, a member of the IL17 cytokine family, promotes the accumulation of a lineage-negative (Lin(-)) multipotent progenitor (MPP) cell population in the gut-associated lymphoid tissue that promotes T(H)2 cytokine responses. The IL25-elicited cell population, termed MPPtype2 cells, was defined by the expression of Sca-1 (also known as Ly6a) and intermediate expression of c-Kit (c-Kit(int)), and exhibited multipotent capacity, giving rise to cells of monocyte/macrophage and granulocyte lineages both in vitro and in vivo. Progeny of MPPtype2 cells were competent antigen presenting cells, and adoptive transfer of MPPtype2 cells could promote T(H)2 cytokine responses and confer protective immunity to helminth infection in normally susceptible Il25(-/-) mice. The ability of IL25 to induce the emergence of an MPPtype2 cell population identifies a link between the IL17 cytokine family and extramedullary haematopoiesis, and suggests a previously unrecognized innate immune pathway that promotes T(H)2 cytokine responses at mucosal sites.

Purpose: To explore the characteristics of rejection of Wuzhishan (WZS) pig-to-rhesus monkey corneal transplants and to evaluate WZS pig corneas as potential donor material for a clinical setting. Methods: Wuzhishan pigs were used as donors and rhesus monkeys as recipients for corneal xenotransplantation. Eighteen rhesus monkeys were divided into three groups. Groups 1 and 2 underwent penetrating corneal xenotransplantation, while group 3 underwent lamellar corneal xenotransplantation. Only group 2 received subconjunctival injections with betamethasone for 3 months. All xenografts were evaluated by slit-lamp microscopy. Two recipients in each group were killed for corneal histopathological staining at 30 days after surgery. The concentrations of cytokines in the aqueous humor were detected by cytometric bead array. Results: Rejection of the xenografts occurred at approximately 15 days after surgery in group 1. Rejection was delayed for more than 4 months by conjunctival injection with betamethasone (group 2). Use of lamellar corneal xenografts (group 3) maintained corneal transparency for more than 3 months. Histopathological examination in group 1 showed that the xenografts were infiltrated with inflammatory cells. The corneal endothelia were destroyed and exudative membranes were formed in the anterior chamber. However, in the betamethasone-treated group, the corneal xenografts showed only minimal edema and almost no inflammatory cell infiltrate. The corneal endothelia were intact and there was no exudative membrane formation. The concentration of interleukin (IL)4, IL5 and IL10 showed an increased shift 3 weeks after surgery in group 1 and 2, but no change of cytokine's concentration was found in group 3. Conclusions: Rejection of pig-rhesus xenografts occurred early in penetrating corneal transplantation, but not in lamellar corneal transplantation. The endothelium of the xenograft might be a primary target of immune attack. Corticosteroid treatment inhibited rejection of the corneal xenografts.