Given the impaired

regulation of antigen presentation and

Given the impaired

regulation of antigen presentation and T-cell proliferation in the absence of CD37 in vitro, one might predict an exaggeration of in vivo adaptive cellular immunity in CD37−/− mice. However, CD37−/− mice show no increased susceptibility to autoimmune induction and conversely, when combined with Tssc6 (Tspan32) deficiency, showed increased susceptibility to the mouse malarial parasite Plasmodium yoelii and poor antigen-specific T-cell responses to influenza infection [16]. It is clear from these findings that data derived in vitro are not predictive of the role of CD37 in immune responses INCB024360 mw in vivo. In this study we examined the role of CD37 in in vivo adaptive cellular immune responses. CD37−/− mice were challenged with live and irradiated tumors, and soluble antigens coupled to the membrane-translocating peptide penetratin — all immunogens known to elicit powerful IFN-γ T-cell responses in WT mice. We show that CD37−/− mice make poor CD4+ and CD8+ T-cell IFN-γ responses to both tumor and model antigen challenge. Furthermore, we present evidence that CD37 ablation impairs various aspects of DC function including cell migration and adhesion. This study demonstrates that a defect in DC migration is a major cellular impairment that underlies poor cell-mediated and anti-tumor responses in CD37−/− mice. Studies of pathogen resistance

Acalabrutinib molecular weight in CD37−/− mice suggested a role for CD37 during development of antigen-specific T-cell responses [16]. Since antigen-specific effector T cells are a critical requirement for tumor elimination [17], rejection of a syngeneic lymphoma-derived cell line transfected with the human cancer antigen Mucin 1 (RMA-Muc1) was compared between WT and CD37−/− mice. While RMA cells grow unchecked in mice of a C57BL/6 (WT) background (Fig. 1A), RMA-Muc1 cells provoke antigen-specific

T-cell responses and tumor rejection typically within 2 weeks [18]. However, CD37−/− Carnitine palmitoyltransferase II mice challenged with RMA-Muc1 failed to reject these tumors over a similar time course (Fig. 1B). Similarly, when challenged with fewer RMA-Muc1 cells, tumors grew significantly larger in CD37−/− mice than in their WT counterparts (Fig. 1C), indicating a role for CD37 in antitumor responses. To compare development of antitumor T-cell responses in WT and CD37−/− mice, γ-irradiated RMA-Muc1 cells were injected i.d. and ELISPOT analyses performed 2 weeks later. While overall splenocyte numbers and leucocyte population frequencies did not differ between WT and CD37−/− mice (Supporting Information Fig. 1), the frequency of Muc1-specific IFN-γ-producing T cells induced in CD37−/− mice was significantly lower than that of WT mice (Fig. 2A), correlating with increased tumor growth observed in CD37−/− mice after RMA-Muc1 tumor challenge (Fig. 1).

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