title: Role of cellular immunity in systemic sclerosis pathogenesis: update on CD4+T cells population studies.
abstract: Immunologic abnormalities observed in Systemic Sclerosis (SSc) patients consist of chronic mononuclear cell infiltration of affected tissues, dysregulation of lymphokine and growth factor production, and autoantibodies production. Expansion of CD4+T cells within the tissue seems to involve their activation that precedes this process. Therefore, CD4+T cells activation, as an early immune event, appears to be an important process in the development and maintaining of SSc. In SSc the disturbance of peripheral tolerance mechanisms could be also responsible for CD4+T cells activation. Consequently, we reevaluated CD4+T cells positive for CD25, GITR, CTLA-4, CD45RO, or Foxp3 in SSc patients, by comparison with healthy donors (HDs), and in correlation with clinical features of the disease. Our results reargued for activation of peripheral blood CD4+T cells in SSc patients. Thus, increased percentages of CD25+ and GITR+ CD4+T cells were found in SSc patients by comparison with HDs. Direct correlation between the percentage of GITR+CD4+T cells and disease activity recommended these cells as a good candidate for disease progression. In SSc patients, the negative regulators of T cells activation are also affected. Thus, CTLA-4+ and Foxp3+ CD4+T cell percentages were significantly reduced in SSc patients when compared to HDs. Indirect correlation between the percentage of CD152+CD4+T cells and autoantibodies (aScl70) presence or disease type highlighted the role of these cells in the disturbance of peripheral tolerance. The absence of the direct correlation between CD152+CD4+T cells and CD45RO+CD4+T cells, correlation observed only in HDs, raised the hypothesis that in SSc patients, memory T cells can be easily activated, and by consequence, they can enter within affected tissues. These data reconfirm the activation state of SSc CD4+T cells and point out some abnormalities in peripheral tolerance mechanisms that can contribute to SSc pathogeny.
authors.affiliation: Department for Advanced Studies, Cellular Receptors Laboratory, Cantacuzino National Institute of Research and Development for Microbiology and Immunology, Bucharest, Romania.
authors.forename: Alina Nicoleta
authors.initials: AN
authors.lastname: Beşliu
authors.forename: Leontina Mirela
authors.initials: LM
authors.lastname: Bănică
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Lonescu
authors.forename: Denisa
authors.initials: D
authors.lastname: Predeţeanu
authors.forename: Crina
authors.initials: C
authors.lastname: Stăvaru
authors.forename: Carmen Maria
authors.initials: CM
authors.lastname: Marica
authors.forename: Cristina
authors.initials: C
authors.lastname: Chiţonu
authors.forename: Gina
authors.initials: G
authors.lastname: Pistol
authors.forename: Maria
authors.initials: M
authors.lastname: Stefănescu
authors.forename: Cristiana
authors.initials: C
authors.lastname: Matache
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D060908:CTLA-4 Antigen; D018450:Disease Progression; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007156:Immunologic Memory; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053450:Glucocorticoid-Induced TNFR-Related Protein; D053645:Interleukin-2 Receptor alpha Subunit; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human