Measurement of CD4+ and CD8+ T-Lymphocyte Cytokine Secretion and Gene Expression Changes in p-Phenylenediamine Allergic Patients and Tolerant Individuals

被引：29

作者：

Coulter, Eve M. ^{[1
]}

Jenkinson, Claire ^{[1
]}

Farrell, John ^{[1
]}

Lavergne, Sidonie N. ^{[1
]}

Pease, Camilla ^{[2
]}

White, Andrew ^{[2
]}

Aleksic, Maja ^{[2
]}

Basketter, David ^{[2
]}

Williams, Dominic P. ^{[1
]}

King, Clodagh ^{[3
]}

Pirmohamed, Munir ^{[1
]}

Park, B. Kevin ^{[1
]}

Naisbitt, Dean J. ^{[1
]}

机构：

[1] Univ Liverpool, Dept Pharmacol, MRC, Ctr Drug Safety Sci, Liverpool L69 3GE, Merseyside, England

[2] Unilever Res, SEAC Toxicol Lab, Bedford, England

[3] Univ Liverpool, Dept Dermatol, Liverpool L69 3GE, Merseyside, England

来源：

JOURNAL OF INVESTIGATIVE DERMATOLOGY | 2010年 / 130卷 / 01期

基金：

英国医学研究理事会;

关键词：

NECROSIS-FACTOR-ALPHA; LATE-PHASE REACTION; CONTACT HYPERSENSITIVITY; HUMAN CD4(+); CELL-RECEPTOR; MAST-CELLS; SENSITIZATION; CD8(+); ANTIGEN; NICKEL;

D O I：

10.1038/jid.2009.187

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100227 [皮肤病学];

摘要：

Factors predisposing to individual susceptibility to contact allergic dermatitis are ill defined. This study was designed to characterize the response of allergic and tolerant individuals' T-lymphocytes after exposure to p-phenylenediamine (PPD). Peripheral blood mononuclear cells (PBMCs) from allergic patients proliferated when treated with PPD and Bandrowski's base (BB) and secreted IL-1 alpha, -1 beta, -4, -5, -6, -8, -10, and -13; IFN-gamma; tumor necrosis factor-alpha; MIP-1 alpha/beta; MCP-1 (monocyte chemotactic protein-1); and RANTES. PBMCs from tolerant individuals were stimulated to proliferate only with BB, and they secreted significantly lower levels of Th2 cytokines. Principal component analysis showed that genes are differentially expressed between the patient groups. A network-based analysis of microarray data showed upregulation of T helper type 2 (Th2) gene pathways, including IL-9, in allergic patients, but a regulatory gene profile in tolerant individuals. Real-time PCR confirmed the observed increase in Th2 cytokine gene transcription in allergic patients. Purified CD4+ and CD8+ T cells from allergic patients were stimulated to proliferate and secrete Th2 cytokines following antigen exposure. Only CD4+ T cells from tolerant individuals were stimulated by BB, and levels of Th2 cytokines were 80% lower. The nature of the antigenic determinant stimulating PBMCs and levels of Th2 cytokines, including IL-9, was confirmed in a validation cohort. These studies show increased activity of Th2 cytokines in CD4+ and CD8+ T cells from individuals with allergic contact dermatitis.

引用

页码：161 / 174

页数：14

共 48 条

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T helper (Th) 2 predominance in atopic diseases is due to preferential apoptosis of circulating memory/effector Th1 cells [J].