Measurement of CD4+ and CD8+ T-lymphocyte cytokine secretion and gene expression changes in p-phenylenediamine allergic patients and tolerant individuals.
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-1alpha, -1beta, -4, -5, -6, -8, -10, and -13; IFN-gamma; tumor necrosis factor-alpha; MIP-1alpha/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.
Coulter
Eve M
EM
Department of Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
Jenkinson
Claire
C
Farrell
John
J
Lavergne
Sidonie N
SN
Pease
Camilla
C
White
Andrew
A
Aleksic
Maja
M
Basketter
David
D
Williams
Dominic P
DP
King
Clodagh
C
Pirmohamed
Munir
M
Park
B Kevin
BK
Naisbitt
Dean J
DJ
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D017449:Dermatitis, Allergic Contact / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism; D016906:Interleukin-9 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010655:Phenylenediamines / Q000009:adverse effects / Q000276:immunology; D012882:Skin Tests; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014373:Tuberculin / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
D016207:Cytokines; C508599:IL5 protein, human; C508607:IL9 protein, human; D018793:Interleukin-13; D015848:Interleukin-5; D016906:Interleukin-9; D010655:Phenylenediamines; D014373:Tuberculin; C051597:Bandrowski's base; C029728:4-phenylenediamine