title: Influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses.
abstract: We have studied the influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses. In a double-blind, placebo-controlled trial of immunotherapy in 40 adult hay fever sufferers, clinical improvement was accompanied by a decrease in the size of the late-phase skin response. When the immunotherapy-treated group was compared with the placebo group, analysis of skin biopsies obtained 24 h after intradermal allergen revealed a significant reduction in the number of infiltrating CD3+ (P = 0.04) and CD4+ (P = 0.009) cells and a trend for a decrease in EG2+ eosinophils (P = 0.08). Treatment did not influence allergen-induced recruitment of CD8+ cells, neutrophils, or macrophages. Unexpected increases in expression of CD25 (P = 0.006) and HLA-DR (P = 0.007) were observed in the actively treated group. In situ hybridization using a panel of riboprobes demonstrated "TH2-type" (IL-4, IL-5) cytokine mRNA responses in both groups of patients. In contrast, significant hybridization for IL-2 (8/16 patients, P = 0.02) and for interferon-gamma (6/16 patients, P = 0.04) was observed only in the actively treated group. These findings indicate that immunotherapy is associated with suppression of allergen-induced CD4+ T lymphocyte infiltration, but among the cells that are recruited, there is upregulation of CD25 and HLA-DR. At least in this model, immunotherapy does not appear to affect expression of TH2-pattern cytokines in response to allergen exposure, but expression of mRNA for Th1-type cytokines was enhanced in half of the patients. The results support the view that immunotherapy may possibly be working through induction of T cell tolerance.
authors.affiliation: Department of Allergy and Clinical Immunology, National Heart & Lung Institute, London, United Kingdom.
authors.forename: V A
authors.initials: VA
authors.lastname: Varney
authors.forename: Q A
authors.initials: QA
authors.lastname: Hamid
authors.forename: M
authors.initials: M
authors.lastname: Gaga
authors.forename: S
authors.initials: S
authors.lastname: Ying
authors.forename: M
authors.initials: M
authors.lastname: Jacobson
authors.forename: A J
authors.initials: AJ
authors.lastname: Frew
authors.forename: A B
authors.initials: AB
authors.lastname: Kay
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis*; D004311:Double-Blind Method; D005260:Female; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D006109:Poaceae; D011058:Pollen / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D012867:Skin / Q000276:immunology*; D012882:Skin Tests
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; D007378:Interleukins; D012333:RNA, Messenger; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor