Evidence of enhanced recombinant interleukin-2 sensitivity in thymic lymphocytes from patients with myasthenia gravis: possible role in autoimmune pathogenesis.
We evaluated the activation state of thymic lymphocytes in patients with myasthenia gravis (MG) by cytofluorographic analysis of CD25 expression and by testing their sensitivity to recombinant interleukin-2 (rIL-2) in the absence of any known previous stimulation. We detected no phenotypic signs of activation in fresh MG thymic lymphocyte suspensions, while functional signs of activation were reflected in a significantly higher sensitivity to rIL-2 in MG patients than in controls. The responses to rIL-2 were time- and dose-dependent, were inhibited by a blocking anti-IL-2 receptor antibody, and were associated with an increase in CD25+ T cells in both patients and controls. The T cells with functional signs of previous activation may represent autoreactive cells involved in the autoimmune process and confirm thymus gland hyperactivity in MG. These cells could result from primary autosensitization against the thymic acetylcholine receptor (AChR)-like molecule or from altered migration of peripheral activated cells into an abnormal thymic environment. Our results also provide a clue for understanding the effect of thymectomy in myasthenia gravis.
Cohen-Kaminsky
S
S
Centre Chirurgical Marie-Lannelongue, Laboratoire d'Immunologie, C.N.R.S. URA-D1159, Le Plessis-Robinson, France.
Levasseur
P
P
Binet
J P
JP
Berrih-Aknin
S
S
D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D009157:Myasthenia Gravis / Q000209:etiology / Q000276:immunology*; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013945:Thymoma / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology; D013953:Thymus Neoplasms / Q000276:immunology
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins