B and T cells also showed altered secretion of cytokines and chemokines after LL-37 and LPS treatment compared with LPS alone 14. In B cells, LL-37 limited class switching and cell proliferation after LPS/IFN-γ treatment 15. Immunizing mice with OVA and mCRAMP led to an increase in specific anti-OVA

IgG as compared with immunization with OVA alone 13, while a fusion of LL-37 and M-CSFRJ6-1 improved the specific immune response to tumors in BGB324 mw mice 16. The extent to which these responses are influenced by APCs and innate immunity is still unclear and many aspects of the relationship between cathelicidins and the adaptive response are largely unknown. Additionally, most in vivo studies have focused on injecting cathelicidin into rodents instead of examining its endogenous effects on adaptive immunity. A study by Kin et al. 17 in this issue of the European Journal of Immunology brings new understanding to the role of cathelicidins in adaptive immunity by isolating populations of B and T cells

from peritoneal lavage and the spleen in WT and Camp−/− mice lacking the gene for mCRAMP. Intriguingly, it was found that the response to, and expression of, IL-4 was altered in the Camp−/− mice and this affected both T and B cells. IL-4 is a key regulator of adaptive immunity that leads to an increased humoral response by promoting Th2 cell development 18. Under IL-4-induced

PF-562271 Dichloromethane dehalogenase Th2 conditions, IL-4 was significantly increased in the Camp−/− T cells and the expression was reduced to WT levels when mCRAMP was added. In contrast, CD4+ T cells from Camp−/− mice showed a similar expression of IFN-γ as WT CD4+ T cells when both were cultured under IFN-γ-induced Th1 conditions 17. IL-4 also enhances class switching in B cells, increasing IgG1 and IgE expression in mice 19. In the Kin et al. study 17, B cells isolated from WT and Camp−/− mice showed no differences in IgM and IgG3 expression when cultured with LPS, or in IgG2c levels when CD40L/IFN-γ was used as a stimulus. Surprisingly, when the B cells were cultured with CD40L/IL-4, the Camp−/− cells showed decreased IgG1 and IgE expression. The antibody levels were restored to those of WT cells when mCRAMP was included in the culture conditions. The decreased IgG1 production was determined to be from reduced mRNA expression rather than changes in class switching. Kin et al. 17 further demonstrated a relationship between mCRAMP and B and T cells by injecting mice with type 1 and 2 antigens or T-cell-dependent antigens 17. T-cell-dependent antigens require Th2 cells to activate B cells and produce antibody, whereas type 1 and 2 antigens are T-cell independent and do not require a Th2 signal.