Influence of human recombinant interferon-alpha2a (rhIFN-alpha2a) on altered lymphocyte subpopulations and monocytes in Behcet's disease.
OBJECTIVE
In Behçet's disease (BD), several abnormalities of lymphocyte subpopulations have been described. Standard treatment comprises immunosuppressive drugs. We successfully treated 50 patients with ocular BD with interferon-alpha2a (IFN-alpha2a) (response rate 92%), although this is counterintuitive because IFN-alpha is immunostimulatory and can sometimes even induce autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis. The aim of the present study was to elucidate the immunomodulatory effects that IFN-alpha might exert on peripheral blood mononuclear cells (PBMC) in BD by examining changes in the distribution of lymphocyte subpopulations under IFN-alpha2a treatment.


METHODS
Fourteen patients with ocular BD were evaluated before and at weeks 4 and 24 of IFN-alpha treatment and compared with 10 healthy controls. PBMC were stained with monoclonal antibodies and measured by flow cytometry.


RESULTS
Compared with the controls there is a significant elevation of monocytes (CD14(+)), CD8(+)/gammadelta T cells, CD3(+)/gammadelta T cells, natural killer (NK) cells (CD56(+)/CD16(+)) and activated/regulatory T cells (CD4(+)/CD25(+) and CD8(+)/CD25(+)) in patients with active BD before treatment with IFN-alpha2a. Numbers of naïve T cells (CD8(+)/CD45(+)RA(+)/RO(-), CD4(+)/CD45(+)RA(+)/RO(-)) were significantly lower. Under therapy, NK cells, CD8(+)/gammadelta T cells and CD3(+)/gammadelta T cells decreased significantly, whereas B cells increased. The previously reduced expression of HLA class I on monocytes in HLA-B51-positive patients rose to levels comparable to HLA-B51-negative patients.


CONCLUSIONS
These results implicate the participation of NK cells and gammadelta T cells, especially CD8(+)/gammadelta T cells, in the pathogenesis of BD and may explain one mechanism by which IFN-alpha2a exerts therapeutic effects. Alternatively, they may result indirectly from remission induction by IFN-alpha2a. The reduced expression of HLA class I on monocytes in HLA-B*51-positive patients might reflect an impaired expression of and antigen presentation by HLA-B*51.
Treusch
M
M
Department of Internal Medicine II (Hematology/Oncology/Immunology/Rheumatology), University Hospital, Otfried-Müller Strasse 10, D-72076 Tübingen, Germany.
Vonthein
R
R
Baur
M
M
Günaydin
I
I
Koch
S
S
Stübiger
N
N
Eckstein
A K
AK
Peter
H-H
HH
Ness
T
T
Zierhut
M
M
Kötter
I
I
D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001528:Behcet Syndrome / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015235:HLA-B Antigens; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D015703:Antigens, CD; D015235:HLA-B Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins