Cathelin-related antimicrobial peptide differentially regulates T- and B-cell function.

Academic Article

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.
  • Published In

    Keywords

  • Animals, Anti-Bacterial Agents, Antimicrobial Cationic Peptides, B-Lymphocyte Subsets, B-Lymphocytes, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cathelicidins, Enzyme-Linked Immunosorbent Assay, Enzyme-Linked Immunospot Assay, Female, Flow Cytometry, Immunoglobulin E, Immunoglobulin G, Immunoglobulin M, Interleukin-4, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Transgenic, Ovalbumin, RNA, Messenger
  • Digital Object Identifier (doi)

    Pubmed Id

  • 18777168
  • Author List

  • Kin NW; Chen Y; Stefanov EK; Gallo RL; Kearney JF
  • Start Page

  • 3006
  • End Page

  • 3016
  • Volume

  • 41
  • Issue

  • 10