title: Perforin expression by CD4+ regulatory T cells increases at multiple sclerosis relapse: sex differences.
abstract: Multiple sclerosis (MS) represents the leading cause of neurological deficit among young adults, affecting women more frequently than men. In MS, the extent of central nervous system lesions is determined by the net balance between self-reactive and regulatory T-cells at any given time, among other factors, as well as by the effect of inflammatory response. Here, we studied both CD4+ and CD8+ T(Reg) in parallel in blood and CSF during MS relapse. A recruitment of both regulatory CD4+ and CD8+ T cells (T(Reg)) within the cerebrospinal fluid (CSF) takes place during MS relapse. Not previously described, the presence of CD4+ T(Reg) in CSF was higher in women than in men, which could account for the sexual dimorphism in the incidence of MS. A direct correlation between plasma oestradiol (E2) and IL-2 levels was observed, in line with a putative circuit of E2 and perforin expression by CD4+ T(Reg) playing a role in MS. Also, serum IFN-alpha was higher in females, with direct correlation with serum E2 levels. This is the first study to analyze perforin expression by CD4+ T(Reg) in MS, which was greatly enhanced in CSF, what points out a relevant role of this molecule in the suppressive effects of the CD4+ T(Reg) in MS, and contributes to the understanding of MS pathophysiology.
authors: Department of Immunology, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, Madrid 28007, Spain.
authors: Marta
authors: M
authors: Tejera-Alhambra
authors: Department of Immunology, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, Madrid 28007, Spain.
authors: Bárbara
authors: B
authors: Alonso
authors: Department of Immunology, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, Madrid 28007, Spain.
authors: Roseta
authors: R
authors: Teijeiro
authors: Department of Immunology, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, Madrid 28007, Spain.
authors: Rocío
authors: R
authors: Ramos-Medina
authors: Department of Immunology, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, Madrid 28007, Spain.
authors: Carol
authors: C
authors: Aristimuño
authors: Department of Immunology, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, Madrid 28007, Spain.
authors: Larissa
authors: L
authors: Valor
authors: Department of Neurology, General University Hospital Gregorio Marañón, Doctor Esquerdo 46, Madrid 28007, Spain.
authors: Clara
authors: C
authors: De Andrés
authors: Department of Immunology, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, Madrid 28007, Spain.
authors: Silvia
authors: S
authors: Sánchez-Ramón
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D004958:Estradiol / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016898:Interferon-alpha / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000134:cerebrospinal fluid; D054353:Perforin / Q000097:blood* / Q000134:cerebrospinal fluid; D012008:Recurrence; D012737:Sex Factors; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D055815:Young Adult
chemical_list: C508594:IL2 protein, human; D016898:Interferon-alpha; D007376:Interleukin-2; D054353:Perforin; D004958:Estradiol