The defect of the perforin granule system in cytotoxic T lymphocytes of atopic patients--are perforin reduction and hyperreleasability of clinical relevance?
Perforin-containing lytic granules are secretory lysosomes of cytotoxic lymphocytes. They act as a negative regulator of activated T cells, control immunoglobulin production, contribute to the regulation of the TH1/TH2 balance, and occupy a central role in anti-viral defense mechanisms. This review focuses on recent evidence for a fundamental defect in the lymphocytic perforin system of atopic patients, namely perforin reduction and the hyperreleasability of perforin granules. These findings are set in relation to the immune imbalance in atopy, which is characterized by a weakly restrained proliferation of allergen-specific T and B cells, a predominance of Ttype-2 cytokines, and an increased susceptibility to cutaneous infections. In the context of the wellknown defect of secretory lysosomes in mast cells and keratinocytes of atopic patients, the possibility of a cell type-independent major pathological factor in atopy is discussed: pan-cellular reduction and hyperreleasability of secretory lysosomes.
Ambach
Andreas
A
Department of Dermatology and Venereology, Otto-von-Guericke-University Magdeburg, Germany. Andreas.Ambach@Medizin.Uni-Magdeburg.de
Bonnekoh
Bernd
B
Gollnick
Harald
H
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015331:Cohort Studies; D003594:Cytoplasmic Granules / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003876:Dermatitis, Atopic / Q000209:etiology / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000209:etiology / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D016131:Lymphocyte Subsets / Q000276:immunology; D008247:Lysosomes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013577:Syndrome; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007073:Immunoglobulin E