title: Expression of Th1, Th2, lymphocyte trafficking and activation markers on CD4+ T-cells of Hymenoptera allergic subjects and after venom immunotherapy.
abstract: Systemic reactions to Hymenoptera stings can be fatal and represent a reduction in the quality of life. The immune mechanisms involved in venom allergic subjects are barely known. Nevertheless, a shift towards a Th1-type response with an increase in IFNγ levels has been observed after venom immunotherapy (VIT). There is currently no information available about the expression of markers on CD4+ T-cells or their involvement in venom allergy, nor following VIT. For this, we have studied the expression of Th1 and Th2-cell markers, homing receptors and activation markers on CD4+ T-cells of subjects who presented systemic allergic reactions, mainly to Polistes dominulus, and after receiving a 4-month conventional VIT protocol. The markers studied were: CD26 (Th1), CD30 (Th2), CXCR4, CXCR3 (Th1), CCR4 (Th2), CD154 (CD40L), CD152 (CTLA-A), and ICOS. We also determined the IL-4 (Th2) and IFNγ (Th1) intracellular cytokine levels in T-cells and carried out a basophil activation test (BAT). Comparing venom allergic subjects with non-allergic healthy controls, we have found up-regulation of CD26, CXCR4, CXCR3, CD154 and ICOS. Conversely, a down-regulation of CD30, CD154 and CD152 occurred upon immune intervention, whereas the remaining markers were not affected. Equally, VIT has been shown to be effective, as evidenced by the decrease of basophil degranulation and increase of IFNγ levels in T-cells after the fourth month of treatment. These new findings highlight the possible application of these surface molecules as markers to distinguish between symptomatic and asymptomatic subjects sensitized to Hymenoptera venom, as well as revealing information about the immune changes associated with VIT.
authors.affiliation: Immunology Section, Servicio de Análisis Clínicos, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain. Electronic address: carmenmcabrera@gmail.com.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Cabrera
authors.affiliation: Immunology Section, Servicio de Análisis Clínicos, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Urra
authors.affiliation: Allergy Section, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Alfaya
authors.affiliation: Allergy Section, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
authors.forename: Federico De La
authors.initials: Fde L
authors.lastname: Roca
authors.affiliation: Allergy Section, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Feo-Brito
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001180:Arthropod Venoms / Q000276:immunology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003888:Desensitization, Immunologic; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006927:Hymenoptera / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007299:Insect Bites and Stings / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D001180:Arthropod Venoms; D015415:Biomarkers
keywords: Costimulatory activation marker; Homing-receptor; Hymenoptera allergy; Non-costimulatory activation marker; T-cell marker; Venom immunotherapy