T helper (Th) 2 predominance in atopic diseases is due to preferential apoptosis of circulating memory/effector Th1 cells.
T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated, Th2-biased peripheral immune response appears to be an important pathogenetic factor. In atopic dermatitis, circulating cutaneous lymphocyte-associated antigen-bearing (CLA+) CD45RO+ T cells with skin-specific homing property represent an activated memory/effector T cell subset. They express high levels of Fas and Fas ligand and undergo activation-induced apoptosis. The freshly purified CLA+ CD45RO+ T cells of atopic individuals display distinct features of in vivo-triggered apoptosis such as pro-caspase degradation and active caspase-8 formation. In particular, the Th1 compartment of activated memory/effector T cells selectively undergoes activation-induced cell death, skewing the immune response toward surviving Th2 cells in atopic dermatitis patients. The apoptosis of circulating memory/effector T cells was confined to atopic individuals whereas non-atopic patients such as psoriasis, intrinsic-type asthma, contact dermatitis, intrinsic type of atopic dermatitis, bee venom allergic patients, and healthy controls showed no evidence for enhanced T cell apoptosis in vivo. These results define a novel mechanism for peripheral Th2 response in atopic diseases.
Akdis
Mübeccel
M
Swiss Institute of Allergy and Asthma Research (SIAF), Obere Strasse 22, CH-7270 Davos, Switzerland.
Trautmann
Axel
A
Klunker
Sven
S
Daigle
Isabelle
I
Kucuksezer
Umut C
UC
Deglmann
Wolfgang
W
Disch
Rainer
R
Blaser
Kurt
K
Akdis
Cezmi A
CA
D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D017209:Apoptosis; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000473:pathology; D053222:Fas Ligand Protein; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000145:classification; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D017493:Leukocyte Common Antigens