PMID- 19657353 OWN - NLM STAT- MEDLINE DCOM- 20100128 LR - 20181201 IS - 1523-1747 (Electronic) IS - 0022-202X (Linking) VI - 130 IP - 1 DP - 2010 Jan TI - Measurement of CD4+ and CD8+ T-lymphocyte cytokine secretion and gene expression changes in p-phenylenediamine allergic patients and tolerant individuals. PG - 161-74 LID - 10.1038/jid.2009.187 [doi] AB - 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. FAU - Coulter, Eve M AU - Coulter EM AD - Department of Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK. FAU - Jenkinson, Claire AU - Jenkinson C FAU - Farrell, John AU - Farrell J FAU - Lavergne, Sidonie N AU - Lavergne SN FAU - Pease, Camilla AU - Pease C FAU - White, Andrew AU - White A FAU - Aleksic, Maja AU - Aleksic M FAU - Basketter, David AU - Basketter D FAU - Williams, Dominic P AU - Williams DP FAU - King, Clodagh AU - King C FAU - Pirmohamed, Munir AU - Pirmohamed M FAU - Park, B Kevin AU - Park BK FAU - Naisbitt, Dean J AU - Naisbitt DJ LA - eng GR - G0700654/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Invest Dermatol JT - The Journal of investigative dermatology JID - 0426720 RN - 0 (Cytokines) RN - 0 (IL5 protein, human) RN - 0 (IL9 protein, human) RN - 0 (Interleukin-13) RN - 0 (Interleukin-5) RN - 0 (Interleukin-9) RN - 0 (Phenylenediamines) RN - 0 (Tuberculin) RN - 20048-27-5 (Bandrowski's base) RN - U770QIT64J (4-phenylenediamine) SB - IM MH - Adult MH - Aged MH - CD4-Positive T-Lymphocytes/cytology/*immunology/metabolism MH - CD8-Positive T-Lymphocytes/cytology/*immunology/metabolism MH - Cell Division/immunology MH - Cytokines/genetics/*metabolism MH - Dermatitis, Allergic Contact/genetics/*immunology/metabolism MH - Female MH - Gene Expression/immunology MH - Gene Expression Profiling MH - Humans MH - Immune Tolerance/*immunology MH - Interleukin-13/genetics/metabolism MH - Interleukin-5/genetics/metabolism MH - Interleukin-9/genetics/metabolism MH - Male MH - Middle Aged MH - Phenylenediamines/adverse effects/immunology MH - Skin Tests MH - Th2 Cells/immunology/metabolism MH - Tuberculin/adverse effects/immunology MH - Young Adult EDAT- 2009/08/07 09:00 MHDA- 2010/01/29 06:00 CRDT- 2009/08/07 09:00 PHST- 2009/08/07 09:00 [entrez] PHST- 2009/08/07 09:00 [pubmed] PHST- 2010/01/29 06:00 [medline] AID - S0022-202X(15)34540-1 [pii] AID - 10.1038/jid.2009.187 [doi] PST - ppublish SO - J Invest Dermatol. 2010 Jan;130(1):161-74. doi: 10.1038/jid.2009.187.