title: High recombinant interleukin-2 sensitivity of peripheral blood lymphocytes from patients with myasthenia gravis: correlations with clinical parameters.
abstract: Myasthenia Gravis (MG) is an autoimmune disorder of neuromuscular transmission associated with antibodies (Ab) against acetylcholine receptor (AChR). Autoantibody production is a T-cell-dependent phenomenon perhaps caused by aberrant immunoregulation. So far, a possible role for immunoregulatory molecules has not been investigated in the pathogenesis of MG. Since interleukin-2 (IL-2) is able to induce peripheral blood mononuclear cell (PBMC) proliferation without a previous activating signal and to upregulate IL-2-receptor expression, we have evaluated the activation state of PBMC in patients with MG, by cytofluorographic analysis of CD25 expression and by testing their sensitivity to recombinant IL-2 (rIL-2) without any known previous stimulation. We found no significant difference in CD25 expression in a large group of patients compared to controls. However, proliferative responses to rIL-2 were significantly higher in MG patients than in controls. In MG, as in controls, this response was time- and dose-dependent, was inhibited by an anti-IL-2 receptor Ab and correlated with an increased percentage of CD25+ T cells after rIL-2 exposure. The response was greater in patients with a high anti-AChR Ab titer and a severe form of the disease, and in patients tested before thymectomy. Thus blood T cells in MG showed functional signs of preactivation (high sensitivity to rIL-2 alone) without detectable CD25 expression on fresh cells, raising the possibility of aberrant IL-2 receptor regulation and/or expression in MG T cells. Decreased sensitivity to rIL-2 after thymectomy, associated with general clinical improvement, suggests a role for activated cells originating from the thymus in the pathogenesis of MG, and is of clinical relevance in patient follow-up. Our findings also provide a new approach in the study of MG pathogenesis: the search for aberrant immunoregulation mechanisms linked to defects in lymphokine circuits.
authors: Centre Chirurgical Marie-Lannelongue, Laboratoire d'Immunologie, CNRS URA-D1159, Le Plessis Robinson, France.
authors: S
authors: S
authors: Cohen-Kaminsky
authors: C
authors: C
authors: Gaud
authors: E
authors: E
authors: Morel
authors: S
authors: S
authors: Berrih-Aknin
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology* / Q000601:surgery; D010641:Phenotype; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology; D013934:Thymectomy
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2