Increased Spontaneous Ex Vivo Apoptosis and Subset Alterations in Peripheral Blood T Cells from Patients with Multiple Sclerosis

  In order to characterize the immunophenotype and the lymphocyte apoptosis in multiple sclerosis (MS) patients, the peripheral blood lymphocytes of 46 MS patients and 12 healthy volunteers were studied by flow cytometry. Immunophenotypic alterations included significant increases in T CD4+ lymphocytes and reductions in the percentages of CD3+ and CD8+ T cells. After 24 h of culture spontaneous apoptosis was increased in almost T lymphocyte subsets from MS patients and it was significantly higher in those patients who had suffered more than two relapses in the two previous years. The incidence of spontaneous apoptosis was not dependent on FasL-Fas interactions and correlated with the percentages of cells positive for active caspases but not with percentages of Fas+ cells. The increased susceptibility to apoptosis of peripheral blood T lymphocytes from MS patients is difficult to reconcile with the previously proposed role of a defective lymphocyte apoptosis in the pathophysiology of MS.Alfredo Prieto and David Díaz contributed equally to this work and are joint first authors.The GENIO-II Group is composed by Pablo Barreiro from Hospital La Paz, Madrid; Clara de Andrés and Ma Luisa Martínez from Hospital Gregorio Marañón, Madrid; Bonaventura Casanova from Hospital La Fe, Valencia; Juan Antonio García-Merino and Rosario Blanco from Hospital Puerta de Hierro, Madrid; Jesús Martín from Hospital Miguel Servet, Zaragoza; Francisco Coret from Hospital Clínico, Valencia; José Carlos Alvarez-Cermeño and Dr José Francisco Plaza from Hospital Ramón y Cajal, Madrid; Eugenia Vilar, Blanca Felgueroso and Julián Benito from Hospital de Móstoles; Asunción Morales Otal and M^a Cruz Gutiérrez del Olmo from Hospital 12 de Octubre, Madrid.