ABSTRACT
The participation of regulatory T (Treg) cells in B cell-induced T cell tolerance has been claimed in different models. In skin grafts, naive B cells were shown to induce graft tolerance. However, neither the contribution of Treg cells to B cell-induced skin tolerance nor their contribution to the histopathological diagnosis of graft acceptance has been addressed. Here, using male C57BL/6 naive B cells to tolerize female animals, we show that skin graft tolerance is dependent on CD25+ Treg cell activity and independent of B cell-derived IL-10. In fact, B cells from IL-10-deficient mice were able to induce skin graft tolerance while Treg depletion of the host inhibited 100% graft survival. We questioned how Treg cell-mediated tolerance would impact on histopathology. B cell-tolerized skin grafts showed pathological scores as high as a rejected skin from naive, non-tolerized mice due to loss of skin appendages, reduced keratinization and mononuclear cell infiltrate. However, in tolerized mice, 40% of graft infiltrating CD4+ cells were FoxP3+ Treg cells with a high Treg:Teff (effector T cell) ratio (6:1) as compared to non-tolerized mice where Tregs comprise less than 8% of total infiltrating CD4 cells with a Treg:Teff ratio below 1:1. These results render Treg cells an obligatory target for histopathological studies on tissue rejection that may help to diagnose and predict the outcome of a transplanted organ.
Subject(s)
B-Lymphocytes/immunology , Graft Survival/immunology , Skin Transplantation , T-Lymphocytes, Regulatory/immunology , Transplantation Tolerance/immunology , Animals , Female , Flow Cytometry , Forkhead Transcription Factors/immunology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Time FactorsABSTRACT
OBJETIVO: Relatar um caso de menina com doença de Ménétrier. DESCRIÇÃO DO CASO: Menina de dez anos, admitida com história de vômitos, diarréia, distensão e dor abdominal intermitentes há três dias. A suspeita foi apendicite e a paciente foi submetida à laparotomia, com achado de ascite e adenomegalia mesentérica. No pós-operatório, evoluiu com edema generalizado, ascite e derrame pleural. Os exames complementares e a evolução clínica demonstraram tratar-se de doença de Ménétrier. COMENTÁRIOS: O quadro clínico e os exames solicitados (alfa-1-antitripsina fecal aumentada, mucosa gástrica tipo fúndica com moderado grau de hiperplasia do epitélio luminal e foveolar e seriografia com hipertrofia do pregueado mucoso gástrico) confirmaram a doença de Ménétrier.
OBJECTIVE: To report a case of Ménétrier's disease in a girl. CASE DESCRIPTION: A 10-year-old girl was admitted to the hospital with a 3-day history of vomiting, diarrhea, intermittent distension and abdominal pain. Appendicitis was suspected, and patient had a laparotomy which showed only ascites and mesenteric adenomegaly. Generalized edema, ascites and right pleural effusion evolved after the surgery. Menetrier's disease was diagnosed by laboratorial exams and clinical evolution. COMMENTS: Clinical aspects and the increased fecal alpha-1-antitrypsin associated to gastric mucosa of fundic type with moderate level of hyperplasia of lumina and foveola epithelium and serioscopy with hypertrophy of the plica of gastric mucosa confirmed Ménétrier's disease.
