Header

UZH-Logo

Maintenance Infos

Increased activation-induced cell death of high IFN-γ–producing TH1 cells as a mechanism of TH2 predominance in atopic diseases


Akkoc, T; de Koning, P J A; Rückert, B; Barlan, I; Akdis, M; Akdis, C A (2008). Increased activation-induced cell death of high IFN-γ–producing TH1 cells as a mechanism of TH2 predominance in atopic diseases. Journal of Allergy and Clinical Immunology, 121(3):652-658.

Abstract

BACKGROUND: A dysregulated and T(H)2-biased immune response appears to be a key pathogenetic factor in atopic diseases. Increased activation and massive infiltration of T cells in the dermis without any evidence for the expansion of their numbers in peripheral blood characterize atopic dermatitis. OBJECTIVE: To investigate differences and mechanisms of T(H)1 and T(H)2 cell activation-induced cell death (AICD) in atopic disease. METHODS: Naive (CD4(+)CD45(+)RA) and memory (CD4(+)CD45(+)RO) T cells were isolated from healthy and atopic individuals. T(H)1 and T(H)2 subsets were in vitro differentiated. High IFN-gamma-producing T cells and CXCR3(+) T cells were purified, and AICD of isolated cells was determined in addition to expression of apoptosis receptors and caspase activation. RESULTS: T(H)1 cells, particularly their high IFN-gamma-producing fraction, and CXCR3(+) T cells showed significantly increased apoptosis in atopic individuals. During their in vitro differentiation, both T(H)1 and T(H)2 cells of atopic individuals showed increased apoptosis compared with the healthy control group, with a significantly high apoptosis in T(H)1 cells. Increased expression of Fas, Fas-ligand, tumor necrosis factor receptor-II, and caspase activation was detected on T(H)1 cells that underwent apoptosis. Neutralization experiments demonstrated a dominant role of IFN-gamma and Fas-Fas-ligand interaction-mediated suicide in T(H)1 cell AICD. CONCLUSION: Predominant T(H)2 profile in atopic diseases might be a result of the increased tendency to activation and apoptosis of high IFN-gamma-producing T(H)1 cells.

Abstract

BACKGROUND: A dysregulated and T(H)2-biased immune response appears to be a key pathogenetic factor in atopic diseases. Increased activation and massive infiltration of T cells in the dermis without any evidence for the expansion of their numbers in peripheral blood characterize atopic dermatitis. OBJECTIVE: To investigate differences and mechanisms of T(H)1 and T(H)2 cell activation-induced cell death (AICD) in atopic disease. METHODS: Naive (CD4(+)CD45(+)RA) and memory (CD4(+)CD45(+)RO) T cells were isolated from healthy and atopic individuals. T(H)1 and T(H)2 subsets were in vitro differentiated. High IFN-gamma-producing T cells and CXCR3(+) T cells were purified, and AICD of isolated cells was determined in addition to expression of apoptosis receptors and caspase activation. RESULTS: T(H)1 cells, particularly their high IFN-gamma-producing fraction, and CXCR3(+) T cells showed significantly increased apoptosis in atopic individuals. During their in vitro differentiation, both T(H)1 and T(H)2 cells of atopic individuals showed increased apoptosis compared with the healthy control group, with a significantly high apoptosis in T(H)1 cells. Increased expression of Fas, Fas-ligand, tumor necrosis factor receptor-II, and caspase activation was detected on T(H)1 cells that underwent apoptosis. Neutralization experiments demonstrated a dominant role of IFN-gamma and Fas-Fas-ligand interaction-mediated suicide in T(H)1 cell AICD. CONCLUSION: Predominant T(H)2 profile in atopic diseases might be a result of the increased tendency to activation and apoptosis of high IFN-gamma-producing T(H)1 cells.

Statistics

Citations

65 citations in Web of Science®
71 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 24 Feb 2009
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Swiss Institute of Allergy and Asthma Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2008
Deposited On:24 Feb 2009 12:11
Last Modified:06 Dec 2017 18:33
Publisher:Elsevier
ISSN:0091-6749
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.jaci.2007.12.1171
PubMed ID:18328893

Download