The human antimicrobial and chemotactic peptides LL-37 and alpha-defensinsare expressed by specific lymphocyte and monocyte populations

We identified antibacterial components in human T and natural killer (NK) c ells by using freshly isolated lymphocytes enriched for T and NK cells as s tarting material. After growing these lymphocytes for 5 days in the presenc e of interleukin (IL)-2, we isolated and characterized several antibacteria l peptides/proteins from the supernatant-alpha -defensins (HNP 1-3), LL-37, lysozyme, and a fragment of histone H2B-although other active components w ere also present. We then used reverse transcriptase-polymerase chain react ion to search for expression of the gene coding for LL-37 in several B-cell lines, gamma delta T-cell lines, NK clones, and one monocytic cell line, w ith positive results, but found no expression in several alpha beta T-cell lines. The alpha -defensins (HNP 1-3) were also found to be expressed in se veral of these cell lines. To confirm the presence of these antibacterial p eptides in lymphocytes, we localized them to NK, gamma delta T cells, B cel ls, and monocytes/macrophages by using double-staining immunohistochemical analysis of freshly isolated lymphocytes. We also found that primary cultur es of lymphocytes transcribe and secrete LL-37 and that these processes are affected by IL-6 and interferon-gamma. In addition, we demonstrated that L L-37 has chemotactic activity for polymorphonuclear leukocytes and CD4 T ly mphocytes, whereas others have shown chemotactic activity for human alpha - defensins (HNP 1-2). These findings suggest that microbicidal peptides are effector molecules of lymphocytes and that antibacterial activity previousl y shown to be derived from T and NK cells may be partly mediated by the ant ibacterial peptides LL-37 and HNP 1-3. (C) 2000 by The American Society of Hematology.