T1-deficient and T1-Fc-transgenic mice develop a normal protective Th2-type immune response following infection withNippostrongylus brasiliensis

Abstract

The IL-1 receptor-related protein T1 is expressed on the surface of Th2, but not Th1 cells. Studies with anti-T1 monoclonal antibodies have suggested that T1 is critical for development of normal Th2-type responses. To elucidate the role of T1 in vivo, we generated T1deficient mice and a T1-transgenic strain which secretes soluble T1-Fc fusion protein into the serum. These were analyzed for the Th2 immune response induced by infection with the parasitic nematode Nippostrongylus brasiliensis. Although Th2 cytokine production by lymph node cells was similar in all groups of N. brasiliensis-infected mice, a decrease in IL-5 production by lung lymphocytes was detected in both T1-deficient and T1-Fc-transgenic mice compared to control littermates. This difference in IL-5 production did not influence blood eosinophilia, but recruitment of eosinophils into lung tissue, especially in T1-Fctransgenic mice was slightly decreased. However, induction of all other immune parameters was normal and both T1-deficient and T1-Fc-transgenic mice were able to clear the parasite infection within 12 days with kinetics similar to those in control mice. Therefore, in contrast to previous suggestions, we conclude that the T1 protein is not obligatory for normal development of Th2 immune responses.

IL-33 exacerbates antigen-induced arthritis by activating mast cells

“…In vivo, IL-33 injection elicits type II cytokine production and eosinophilia in naïve mice (1,8). However, studies in ST2 Ϫ/Ϫ mice demonstrate that ST2 is not required for IL-4-induced Th2 cell development or function (9)(10)(11), suggesting that ST2/IL-33 may drive type II responses via an alternative pathway or that the function of IL-33/ST2 could extend beyond type II responses. Mast cells express a high density of ST2 and produce a variety of proinflammatory cytokines in vitro in response to IL-33 (1,(12)(13)(14).…”

Regulation and Function of T1/ST2 Expression on CD4+ T Cells: Induction of Type 2 Cytokine Production by T1/ST2 Cross-Linking

“…It is, therefore, tempting to speculate that in vivo depending on the pathogen-induced polarizing cytokine environment, the up-regulation of T1/ST2 expression on T cells by cytokines such as IL-6 favors the differentiation of naive Th cells into Th2 cells. It is clear, however, that Th2 development can occur in vivo even in the absence of T1/ST2 (23)(24)(25).…”

Characterization of Signaling Pathways Activated by the Interleukin 1 (IL-1) Receptor Homologue T1/ST2

“…In addition to being a stable cell marker on Th2 cells, T1/ST2 has been shown to be important in Th2 effector function since treatment of mice with a monoclonal antibody against T1/ST2 inhibited allergic airway inflammation in response to both allergen provocation and viral antigen (9,10). Studies on T1/ST2-deficient mice, however, have yielded conflicting evidence as to the functional role of T1/ST2 (11)(12)(13).…”