Circulating CD4+CD25+ and CD4+CD25+ T cells in myasthenia gravis and in relation to thymectomy.
Studies in experimental animal models of human autoimmune diseases have revealed that CD4(+)CD25(+) T regulatory (Tr) cells are of thymic origin and have potentials in preventing auto-aggressive immunity. Myasthenia gravis (MG) is the best-characterized autoimmune disease. Changes in the thymus are found in a majority of patients with MG. Thymectomy has beneficial effects on the disease severity and course in a substantial proportion of MG patients. But the occurrence and characteristics of Tr cells have not yet been defined in MG. We determined the frequencies and properties of circulating CD4(+)CD25(+) versus CD4(+)CD25(-) cells in MG patients and healthy controls (HCs), with special focus on the effect of thymectomy on CD4(+)CD25(+) cells. CD4(+)CD25(high) cells comprise only about 2% of blood lymphocytes in both MG patients and HCs. Frequencies of CD4(+)CD25(high) cells were similar in MG patients irrespective of treatment with thymectomy. CD4(+)CD25(+) cells in both MG patients and HCs are mainly memory T cells and are activated to a greater extent than CD4(+)CD25(-) cells, as reflected by high levels of CD45RO and human leucocyte antigen (HLA)-DR-positive cells. In both MG patients and HCs, CD4(+)CD25(+) cells also contained a high proportion of CD95-expressing cells as possible evidence of apoptosis-proneness. Upon stimulation with anti-CD3/CD28 monoclonal antibodies, CD4(+)CD25(+) cells responded more vigorously than CD4(+)CD25(-) cells in MG, irrespective of treatment with thymectomy, as well as in HCs. Although CD4(+)CD25(-) cells are mainly naïve T cells, in non-thymectomized MG patients, they are activated to a greater extent as reflected by higher expression of HLA-DR and CD95 on the surface compared to HCs. The data thus show that there is no deficiency of CD4(+)CD25(+) cells in MG, nor is the proportion of CD4(+)CD25(+) cells influenced by thymectomy.
Huang
Y-M
YM
Immunological Research Unit, Department of Medicine, Centre for Molecular Medicine (CMM), Stockholm, Sweden. yu-min.huang@neurotec.ki.se
Pirskanen
R
R
Giscombe
R
R
Link
H
H
Lefvert
A-K
AK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015704:CD4 Antigens / Q000097:blood / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000097:blood / Q000276:immunology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000097:blood / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013934:Thymectomy; D019014:fas Receptor / Q000097:blood / Q000276:immunology
D015704:CD4 Antigens; D006684:HLA-DR Antigens; D015375:Receptors, Interleukin-2; D019014:fas Receptor; D017493:Leukocyte Common Antigens