Human T cell subset commitment determined by the intrinsic property of antigen: the proteolytic activity of the major mite allergen Der p 1 conditions T cells to produce more IL-4 and less IFN-gamma.
The house dust mite Dermatophagoides pteronyssinus allergen Der p 1 elicits IgE antibody responses in a significant proportion of patients suffering from dust mite allergy. We have recently shown that Der p 1 proteolytically cleaves a cell surface molecule involved in the homeostatic control of human IgE synthesis, namely the IL-2 receptor (CD25) on T cells. As a result, these T cells show markedly diminished proliferation and IFN-gamma secretion in response to stimulation by anti-CD3 antibody. However, these observations still leave open the important issue of whether CD25 cleavage, and the consequent suppression of IFN-gamma secretion, leads to enhanced IL-4 secretion, and whether such cytokine changes would be exhibited by both CD4 and CD8 T cells. Here we demonstrate for the first time that the proteolytic activity of Der p 1 biases human CD4 and CD8 T cells towards a type 2 cytokine profile. Our data provide compelling evidence for the role of the proteolytic activity of Der p 1 in creating a microenvironment conducive for IgE synthesis.
Ghaemmaghami
A M
AM
Division of Molecular and Clinical Immunology, Faculty of Medicine and Health Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, GB.
Robins
A
A
Gough
L
L
Sewell
H F
HF
Shakib
F
F
D000485:Allergens / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D039741:Antigens, Dermatophagoides; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology*; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008925:Mites / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000485:Allergens; D000911:Antibodies, Monoclonal; D039741:Antigens, Dermatophagoides; D006023:Glycoproteins; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma