title: Cathelin-related antimicrobial peptide differentially regulates T- and B-cell function.
abstract: Mammalian antimicrobial peptides (AMPs) play an important role in host defense via direct antimicrobial activity as well as immune regulation. The mouse cathelin-related antimicrobial peptide (mCRAMP), produced from the mouse gene Camp, is the only mouse cathelicidin identified and the ortholog of the human gene encoding the peptide LL-37. This study tested the hypothesis that mouse B and T cells produce and respond to mCRAMP. We show that all mature mouse B-cell subsets, including follicular (FO), marginal zone (MZ), B1a, and B1b cells, as well as CD4(+)  and CD8(+)  T cells produce Camp mRNA and mCRAMP protein. Camp(-/-)  B cells produced equivalent levels of IgM, IgG3, and IgG2c but less IgG1 and IgE, while Camp(-/-)  CD4(+)  T cells cultured in Th2-inducing conditions produced more IL-4-expressing cells when compared with WT cells, effects that were reversed upon addition of mCRAMP. In vivo, Camp(-/-)  mice immunized with TNP-OVA absorbed in alum produced an enhanced TNP-specific IgG1 response when compared with WT mice. ELISpot analysis revealed increased numbers of TNP-specific IgG1-secreting splenic B cells and FACS analysis revealed increased CD4(+)  T-cell IL-4 expression. Our results suggest that mCRAMP differentially regulates B- and T-cell function and implicate mCRAMP in the regulation of adaptive immune responses.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Kin
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.forename: Emily K
authors.initials: EK
authors.lastname: Stefanov
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
authors.forename: John F
authors.initials: JF
authors.lastname: Kearney
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D054804:Cathelicidins / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012333:RNA, Messenger; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin