IL-13 from Th2-type cells suppresses induction of antigen-specific Th1 immunity in a T-cell lymphoma

Abstract

Dalton's lymphoma (DL) is a transplantable T-cell lymphoma of spontaneous origin, characterized by highly invasive and immunosuppressive property. Progression of DL cells results into an imbalance of T helper type 1 (T(h)1)/T helper type 2 (T(h)2)-type cytokine in the host, which is partly responsible for DL-induced severe immunosuppression and DL cell progression. In this study, we have shown the role of IL-13 in the regulation of T(h)1 immunity in both normal healthy and DL-bearing host. IL-13 pre-treatment inhibits the induction of 2,4-dinitro-1-fluorobenzene-induced contact hypersensitivity and delayed-type hypersensitivity (DTH) in antigen-challenged mice, which have been confirmed by neutralizing IL-13 by systemic delivery of non-signaling decoy receptor IL-13Ralpha2. Furthermore, IL-13 neutralization enhances the splenocyte proliferation, which has been inhibited by IL-13 administration. Adoptive transfer of splenocyte from IL-13-pre-treated mice and macrophages incubated with IL-13 and pulsed with antigens suppresses the DTH as well in antigen-challenged recipient mice. In addition, it also suppresses the production of pro-inflammatory cytokine and C-C chemokine in DTH footpad. Furthermore, IL-13 neutralization not only enhances the DTH reaction but also increases longevity and survival of DL-bearing host, which suggests that blocking/inactivating systemic IL-13 enhances T(h)1 immunity, and therefore, effects to diminish IL-13 production may have therapeutic value in a host bearing T-cell lymphoma.

Colitis and Intestinal Inflammation in IL10 Mice Results From IL-13Rα2–Mediated Attenuation of IL-13 Activity

“…In both cases, pro-inflammatory cytokine production was suppressed, either following rIL-13 treatment or following the induction of IL-13 by IL-25, with hepatic Kupfer cells48 and APC’s49 identified as the key targets of IL-13. It has previously been reported that IL-13 can abrogate Th1 development indirectly 50, by modulating APC function (reviewed in 35, 51); however, this is one of the first studies implicating IL-13 as a negative regulator of Th17 development in vivo.…”

Modeling Granulomas in Response to Infection in the Lung

“…IL-2 induces proliferation of Th1 cells [ 15 ]. Both activation and proliferation of Th1 cells are antagonized by IL-13 [ 36 ], while the activation of Th2 cells is antagonized by Th1 [ 18 , 20 , 21 ]. Hence, the equation of Th1 and Th2 cells is given as follows: …”

Permanent protection of PLG scaffold transplanted allogeneic islet grafts in diabetic mice treated with ECDI-fixed donor splenocyte infusions

“…The enhanced IL-13 production is indicative of a tendency of T cells from tolerized mice to polarize towards a Th2 phenotype upon donor stimulation. This phenotype has been associated with down-regulation of Th1 immunity[35] and prolongation of allogeneic graft survival by work from others[36-38]. The role of this cytokine in our model is currently being investigated.…”