ICOS Costimulation Expands Th2 Immunity by Augmenting Migration of Lymphocytes to Draining Lymph Nodes

Abstract

The T cell costimulatory molecule ICOS regulates Th2 effector function in allergic airway disease. Recently, several studies with ICOS−/− mice have also demonstrated a role for ICOS in Th2 differentiation. To determine the effects of ICOS on the early immune response, we investigated augmenting ICOS costimulation in a Th2-mediated immune response to Schistosoma mansoni Ags. We found that augmenting ICOS costimulation with B7RP-1-Fc increased the accumulation of T and B cells in the draining lymph nodes postimmunization. Interestingly, the increased numbers were due in part to increased migration of undivided Ag-specific TCR transgenic T cells and surprisingly B cells, as well as non-TCR transgenic T cells. B7RP-1-Fc also increased the levels of the chemokines CCL21 and CXCL13 in the draining lymph node, suggesting ICOS costimulation contributes to migration by direct or indirect effects on dendritic cells, stromal cells and high endothelial venules. Further, the effects of B7RP-1-Fc were not dependent on immunization. Our data support a model in which ICOS costimulation augments the pool of lymphocytes in the draining lymph nodes, leading to an increase in the frequency of potentially reactive T and B cells.

Inducible Costimulator (ICOS) and ICOS Ligand Signaling Has Pivotal Roles in Skin Wound Healing via Cytokine Production

“…33 Another study showed that transfer of ICOSenriched T cells followed by allergen airway challenge induced infiltration of recipient lymphocytes. 34 Therefore, ICOS-ICOSL signaling is likely important for lymphocyte migration, although direct effects of ICOS on lymphocyte chemotaxis have not yet been examined.…”

The Role of Costimulatory Molecules in Allergic Disease and Asthma

“…Furthermore, this costimulatory molecule has been suggested not only to intensify some of the functions of CD28 during an already established immune response but also to induce additional T-effector cell functions [22]. Recent studies suggest that ICOS-mediated costimulation may regulate TH2-effector cell function without affecting TH2 differentiation [23]. Another study showed that transfer of ICOS-enriched T cells followed by allergen airway challenge induced infiltration of recipient T and B cells as well as local production of allergen-specific IgE by intrapulmonary plasma cells [24].…”

ICOS‐dependent stimulation of NKT cells by marginal zone B cells

“…Therefore, we tested two co-stimulatory molecules -GITR and ICOSL -that can potentially shape NKT-cell responses. GITR had been shown previously to be essential for activation of NKT cells [18], while ICOSL can stimulate CD41 T cells to secrete IL-4 rather than 31].When a blocking anti-GITR antibody was added to the co-cultures of NKT cells with either MZ B cells or cDCs sensitized by aGalCer, NKT-cell proliferation and IL-4 production were not inhibited ( Fig. 6A and C).…”

“…ICOS/ICOSL interaction was shown to have a major role on the expansion of T H 2 responses [23,31]. In vivo blockade of ICOS affects T H 2 effector functions [31,40] and the presence of a functional ICOS/ICOSL pathway was shown to be crucial for the development of T H 2-driven allergic airway disease and the development of allergen-specific T H 2 cells [23,31]. Moreover, T cells isolated from ICOS À/À mice were not able to produce IL-4 [31].…”

“…In vivo blockade of ICOS affects T H 2 effector functions [31,40] and the presence of a functional ICOS/ICOSL pathway was shown to be crucial for the development of T H 2-driven allergic airway disease and the development of allergen-specific T H 2 cells [23,31]. Moreover, T cells isolated from ICOS À/À mice were not able to produce IL-4 [31]. In agreement, we show here that blockage of ICOSL on MZ B cells not only leads to a complete abrogation of NKT-cell proliferation but also inhibits differentiation of NKT cells towards IL-4 production.…”