6533b839fe1ef96bd12a66f8

RESEARCH PRODUCT

Human CD4+CD25+ T cells derived from the majority of atopic donors are able to suppress TH1 and TH2 cytokine production

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Abstract Background: Recently, it has been established that CD4 + CD25 + T cells with regulatory capacity are present in human peripheral blood, inhibiting allogeneic proliferation and cytokine production of preactivated CD4 + CD25 − respond-er T cells. Objective: The aim of this study was to analyze in an allergen-specific setting whether such regulatory CD4 + CD25 + T cells also exist and function normally in atopic individuals, especially concerning the inhibition of T H 2 cytokines. Methods: For this purpose, CD4 + CD25 − or CD4 + CD25 + T cells from donors allergic to grass or birch pollen (mainly with rhinitis) or from healthy nonatopic donors were stimulated in the presence of autologous, mature, monocyte-derived, allergen-pulsed dendritic cells, and the preactivated CD4 + CD25 + T cells were added to CD4 + CD25 − T cells during restimulation. Results: CD4 + CD25 + T cells from the nonatopic donors and from the majority of the patients investigated proliferated poorly, produced fewer cytokines, and inhibited the proliferation and T H 1 (IFN-γ) and T H 2 (IL-4 and IL-5) cytokine production of CD4 + CD25 − T cells but not IL-10 production. The suppression of CD4 + CD25 − T cells by CD4 + CD25 + T cells was at least partially antigen unspecific and not reversible with anti-IL-10, anti-transforming growth factor β, or anti-cytotoxic T lymphocyte–associated antigen 4 mAb but was reversible with IL-2. In some atopic patients preactivated CD4 + CD25 + T cells reproducibly showed strong proliferative responses, produced higher amounts of IL-4 and IL-10 than CD4 + CD25 − T cells, and suppressed only the IFN-γ production of CD4 + CD25 − T cells. Conclusion: These data indicate that regulatory CD4 + CD25 + T cells are present and functional in most atopic patients with allergic rhinitis and are able to inhibit T H 1, as well as T H 2, cytokine production.