Details

Autor(en) / Beteiligte

• Peixoto, Tatiana Vasconcelos
• Carrasco, Solange
• Botte, Domingos Alexandre Ciccone
• Catanozi, Sergio
• Parra, Edwin Roger
• Lima, Thaís Martins
• Ugriumov, Natasha
• Soriano, Francisco Garcia
• de Mello, Suzana Beatriz Verissímo
• Rodrigues, Caio Manzano
• Goldenstein-Schainberg, Cláudia

Titel

CD4 + CD69 + T cells and CD4 + CD25 + FoxP3 + Treg cells imbalance in peripheral blood, spleen and peritoneal lavage from pristane-induced systemic lupus erythematosus (SLE) mice

Ist Teil von

• Advances in rheumatology (London, England), 2019-07, Vol.59 (1), p.30-30, Article 30

Ort / Verlag

England: BioMed Central

Erscheinungsjahr

2019

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Adaptive immune cells, including CD4 CD69 and CD4 CD25 FoxP3 regulatory T (Treg) cells, are important for maintaining immunological tolerance. In human systemic lupus erythematosus (SLE), CD4 CD25 FoxP3 Treg cells are reduced, whereas CD69 expression is increased, resulting in a homeostatic immune imbalance that may intensify autoreactive T cell activity. To analyze the mechanisms implicated in autotolerance failure, we evaluated CD4 CD69 and CD4 CD25 FoxP3 T cells and interleukin profiles in a pristane-induced SLE experimental model. For lupus induction, 26 female Balb/c mice received a single intraperitoneal 0.5 ml dose of pristane, and 16 mice received the same dose of saline. Blood and spleen samples were collected from euthanized mice 90 and 120 days after pristane or saline inoculation. Mononuclear cells from peripheral blood (PBMC), peritoneal lavage (PL) and splenocytes were obtained by erythrocyte lysis and cryopreserved for further evaluation by flow cytometry using the GuavaEasyCyte TM HT. After thawing, cells were washed and stained with monoclonal antibodies against CD3, CD4, CD8, CD25, CD28, CD69, FoxP3, CD14 and Ly6C (BD Pharmingen TM). Interleukins were quantified using Multiplex® MAP. The Mann-Whitney test and the Pearson coefficient were used for statistical analysis, and p < 0.05 considered significant. Compared with the controls, SLE-induced animals presented increased numbers of CD4 CD69 T cells in the blood on T90 and T120 (p = 0.022 and p = 0.008) and in the spleen on T120 (p = 0.049), but there were decreased numbers in the PL (p = 0.049) on T120. The percentage of Treg was lower in blood (p < 0.005 and p < 0.012) on T90 and T120, in spleen (p = 0.043) on T120 and in PL (p = 0.001) on T90. Increased numbers of CD4 + CD69+ T cells in the PL were positively associated with high IL-2 (p = 0.486) and IFN-γ (p = 0.017) levels, whereas reduced Treg cells in the blood were negatively correlated with TNFα levels (p = 0.043) and positively correlated with TGFβ1 (p = 0.038). Increased numbers of CD4 CD69 T cells and reduced numbers of CD4 CD25 FoxP3 Treg cells with an altered interleukin profile suggests loss of autotolerance in pristane-induced lupus mice, which is similar to human lupus. Therefore, this model is useful in evaluating mechanisms of cellular activation, peripheral tolerance and homeostatic immune imbalance involved in human SLE.