Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy.
BACKGROUND
Immunotherapy involves the modulation of allergen-specific T-cell responses, either T(H)2-to-T(H)1 immune deviation or, in bee venom-treated patients, induction of IL-10 production by CD4+CD25+ T cells. IL-10-producing CD4+CD25+ regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology.


OBJECTIVE
The aim of this study was to evaluate the role of IL-10 production and CD4+CD25+ T cells in the response to grass pollen immunotherapy.


METHODS
PBMCs were isolated from patients after 1 year of grass pollen immunotherapy and from matched untreated atopic and healthy control subjects. After 6 days of in vitro stimulation with Phleum pratense, production of IL-10, IL-5, IL-4, and IFN-gamma and proliferation and numbers of CD4+CD25+ T cells were measured. T cells were then stimulated for a further 5 hours with phorbol 12-myristate 13-acetate and ionomycin and assessed for intracellular IL-10 by means of flow cytometry.


RESULTS
Patients undergoing immunotherapy produced significantly more IL-10 than atopic control subjects (patients undergoing immunotherapy, 116 +/- 21 pg/mL [n = 11]; atopic patients, 30 +/- 5 pg/mL [n = 11]; P <.001), and the number of CD4+CD25+ cells identified after allergen stimulation was also greater in the immunotherapy group. The numbers of CD4+CD25+ T cells correlated positively with activation as measured by proliferation in both of the control groups but not in the immunotherapy group. Moreover, only T cells from patients undergoing immunotherapy were positive for intracellular IL-10, and these were almost exclusively CD4+CD25+ cells.


CONCLUSIONS
Grass pollen immunotherapy results in a population of circulating T cells that express the IL-10(+) CD4+CD25+ phenotype in response to allergen restimulation.
Francis
James N
JN
Upper Respiratory Medicine, National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK.
Till
Stephen J
SJ
Durham
Stephen R
SR
D000328:Adult; D000485:Allergens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003888:Desensitization, Immunologic; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D006109:Poaceae / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*
D000485:Allergens; D016207:Cytokines; D015375:Receptors, Interleukin-2; D016753:Interleukin-10