Relative impact of CD4+CD25+ regulatory T cells and tacrolimus on inhibition of T-cell proliferation in patients with atopic dermatitis

Br J Dermatol. 2005 Oct;153(4):750-7. doi: 10.1111/j.1365-2133.2005.06675.x.

Abstract

Background: It has been established recently that CD4+CD25+ regulatory T cells (Tregs) play an important role in controlling various immune responses. Immunosuppressive drugs are often used to treat immune dysregulation but are frequently associated with undesirable side-effects.

Objectives: We examined the suppressive capacity of circulating Tregs in patients with atopic dermatitis (AD). Combined effects of Tregs and tacrolimus on the inhibition of T-cell proliferation in vitro were also assessed.

Methods: CD4+CD25+ and CD4+CD25- T cells were isolated from peripheral blood mononuclear cells using immunomagnetic beads. CD4+CD25- T cells were stimulated with purified protein derivative (PPD) or house dust mite allergen (Der p1) for 6 or 7 days, respectively. A dose range of tacrolimus and CD4+CD25+ T cells were added separately, or together. Proliferation was measured by (3)H-thymidine incorporation.

Results: CD4+CD25+ T cells from normal controls and patients with AD are anergic and inhibit the proliferation of CD4+CD25- T cells in response to PPD and Der p1 in vitro in a dose-dependent manner. Addition of tacrolimus and Tregs together showed significantly stronger inhibition of proliferation than either on their own. This was true for both antigens and both in normal controls and in patients with AD.

Conclusions: CD4+CD25+ T cells in patients with AD have normal suppressive activity compared with healthy controls. Tregs and tacrolimus have additive effects on the inhibition of proliferation in response to PPD and Der p1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Dermatophagoides / immunology
  • Arthropod Proteins
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cysteine Endopeptidases
  • Dermatitis, Atopic / immunology*
  • Humans
  • Immune Tolerance / drug effects
  • Immunosuppressive Agents / pharmacology*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Receptors, Interleukin-2 / blood
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • Tacrolimus / pharmacology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Tuberculin / immunology

Substances

  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Immunosuppressive Agents
  • Receptors, Interleukin-2
  • Tuberculin
  • Cysteine Endopeptidases
  • Dermatophagoides pteronyssinus antigen p 1
  • Tacrolimus