P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflamed tissues

Abstract

When activated, T helper cells differentiate into one of two subsets, Th1 and Th2, characterized by distinct profiles of cytokine production. Th1 cells activate pro-inflammatory effector mechanisms involved in protection and autoimmunity, whereas Th2 cells induce humoral and allergic responses and downregulate local inflammation. Apart from differences in the repertoire of cytokines, no phenotypic attributes are established that distinguish the two subsets. Here we show that Th1 cells, but not Th2 cells, are able to bind to P-selectin and E-selectin. Moreover, only Th1 cells can efficiently enter inflamed sites in Th1-dominated models, such as sensitized skin or arthritic joints, but not in a Th2-dominated allergic response. Immigration of Th1 cells into inflamed skin can be blocked by antibodies against P- and E-selectin. These results provide evidence for adhesion mechanisms to distinguish between the two T helper subsets and mediate their differential trafficking. They indicate that selective recruitment is an additional level of regulation for both effector function profile and character of a local immune response.

Induction of organ‐selective CD4+ regulatory T cell homing

“…As polarizing compounds, RA and IL-12 were used, which have been shown to induce a 4 b 7 and P-lig on activated T cells, respectively [25,26]. In vitro activation of CFSE-labeled naïve-like Treg in the presence of RA induced high a 4 b 7 levels on the vast majority of Treg (Fig.…”

“…Tissuespecific DC have been shown in a number of in vitro and in vivo studies to be involved in the instruction of naïve T cells [4,[17][18][19][20][22][23][24] reported that GALT DC were capable of converting metabolites of dietary vitamin A into retinoic acid (RA), which in turn induced T cell expression of a 4 b 7 and CCR9, leading to the generation of gut-tropic T cells. However, the factors, which are involved in the generation of skin-specific T cell homing in vivo, are largely unknown, although important roles for cytokines including IL-12 and TGF-b have been suggested from in vitro studies [26][27][28]. CD25 + CD4 + Treg play a central role in the maintenance of immunological homeostasis and self-tolerance [29].…”

“…Recently, Iwata et al [25] reported that GALT DC were capable of converting metabolites of dietary vitamin A into retinoic acid (RA), which in turn induced T cell expression of a 4 b 7 and CCR9, leading to the generation of gut-tropic T cells. However, the factors, which are involved in the generation of skin-specific T cell homing in vivo, are largely unknown, although important roles for cytokines including IL-12 and TGF-b have been suggested from in vitro studies [26][27][28].…”

Th1/Th2 cytokine balance in arthritis

“…These changes are associated with increased expression of adhesion molecules, leading to increased cell migration. Migration of Thl cells, rather than Th2 cells, is facilitated through the use of the E and P selectins (52). Thus, expression of such adhesion molecules is mandatory for an increase in the migration of T cells in a non-antigen-specific manner.…”

Interferon‐γ limits Th1 lymphocyte adhesion to inflamed endothelium: A nitric oxide regulatory feedback mechanism

“…Indeed, an association between the induction of the Th1 effector phenotype and P-selectin ligand expression was observed in vitro [3,4]. More recently, however, isolation from lymphoid tissues of already polarized T cells revealed that Th1 and Th2 lymphocytes express similar levels of selectin ligands [5,6].…”