Leukocytic antimicrobial peptides kill autoimmune T cells.
Small antimicrobial peptides are abundantly produced by leukocytes. These peptides are active against a broad range of pathogens, notably bacteria, fungi and enveloped viruses, but hardly anything is known about their physiological and pathophysiological relevance. We observed that indolicidin, and to a lesser extent bactenecin, are strongly cytotoxic to rat and human T lymphocytes, while a variety of other cell lines are not affected by these endogenous antibiotics. The defensins HNP-1, HNP-2 and HNP-3, the structurally related but not bactericidal corticostatin, or cecropin P1 did not affect T lymphocyte viability or proliferation. Thus, indolicidin and bactenecin might function as local regulators inhibiting clonal expansion of T lymphocytes during ongoing immune responses. As immunosuppressive agents in the treatment of autoimmune disease, these peptides appear to be of limited potential, as systemic activity of such peptides is low, and we did not observe significant immunosuppressive effects in experimental autoimmune neuritis or encephalomyelitis.
Institute of Brain Research, Neurological Clinic of Tübingen, Germany.
H J
HJ
Schluesener
S
S
Radermacher
A
A
Melms
S
S
Jung
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D015551:Autoimmunity; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D023082:Defensins; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D008969:Molecular Sequence Data; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects*; D023084:alpha-Defensins
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D023082:Defensins; D010455:Peptides; D010456:Peptides, Cyclic; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C406416:human neutrophil peptide 2; C406427:human neutrophil peptide 3; C073143:indolicidin; C056454:bactenecin