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


OBJECTIVE
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.
Vukmanovic-Stejic
M
M
Department of Immunology and Molecular Pathology, Division of Infection and Immunity, Windeyer Institute of Medical Sciences, University College London, London W1T 4JF, U.K. m.vukmanovic-stejic@ucl.ac.uk
McQuaid
A
A
Birch
K E
KE
Reed
J R
JR
Macgregor
C
C
Rustin
M H A
MH
Akbar
A N
AN
D039741:Antigens, Dermatophagoides / Q000276:immunology; D060829:Arthropod Proteins; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D003876:Dermatitis, Atopic / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000097:blood; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014373:Tuberculin / Q000276:immunology
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D014373:Tuberculin; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1; D016559:Tacrolimus