Consistent with this, splenocytes from Camp−/− mice that had been administered with a T-cell-dependent antigen were also found to have increased IL-4 mRNA expression and increased numbers of CD4+IL-4+ T cells as compared with those from similarly treated WT mice. The connections between mCRAMP and IL-4 open up intriguing possibilities for the role of cathelicidins in adaptive

immunity. In the mice given TNP-OVA/alum and in the in vitro T cells, the responses indicate that mCRAMP suppresses both the development of a Th2 response and the Th2-mediated class switching to IgG1 through IL-4 17, 19. In contrast, Sorafenib mouse the results from isolated B cells stimulated with CD40L/IL-4 indicated that mCRAMP Selleckchem Temozolomide promoted IgG1 production by increasing transcription 17. Kurosaka et al. 13 showed that mCRAMP administered as an adjuvant with OVA increases IL-4 and OVA-specific IgG1 in splenocytes, although the response

was not Th2-mediated. Similarly, An et al. 16 found that LL-37 acts as an effective adjuvant in a vaccine against tumor cells, while Davidson et al. 8 found a bias towards a Th1 response in human DCs. The conflicting reports may reflect methodological differences, such as using Camp−/− mice versus injecting cathelicidin into WT mice, or the timing and nature of other stimuli applied. Nonetheless, these studies indicate that mCRAMP likely mediates its effects on adaptive immunity through many other factors in addition to IL-4. The work by Kin et al. 17 shows that mCRAMP alters B- and T-cell responses, highlighting the novel role of mCRAMP in the T-cell-dependent activation of B cells, and thus providing evidence that mCRAMP and other cathelicidins have a greater role in the adaptive immune response than previously appreciated. However, many questions still remain, particularly whether

mCRAMP acts directly on components of the adaptive immune system or if intermediates are involved. It is also of interest to determine whether the changes seen by Kin et al. 17 in response to T-cell-dependent antigen are due to mCRAMP altering mafosfamide both T and B cells or whether only one cell type is directly involved. The use of conditional knockouts or adoptive transfer to examine when Camp is absent from either T or B cells will help resolve these issues. Similar models could also be used to clarify the functions of APCs in shaping the Camp−/− effects on lymphocytes. Determining the specific cells and pathways altered by mCRAMP will provide further insight into the roles of cathelicidins in bridging innate and adaptive immunity. Funding from the Canadian Institutes for Health Research for the authors own peptide research is gratefully acknowledged. REWH holds a Canada Research Chair. Conflict of interest: The authors have declared no financial or commercial conflict of interest. See accompanying article: http://dx.doi.org/10.1002/eji.