ABSTRACT
Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4+CCR6+IL-7R+T cells from human tonsils produced IL-10 following stimulation by naïve B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6+B helper T cells were phenotypically distinct from follicular helper T (TFH) cells and lacked BCL6 expression. In peripheral blood, a CCR6+T cell population with similar characteristics was identified, which lacked Th17- and TFH-associated gene signatures and differentiation-associated surface markers. CD4+CCR6+T cells expressing IL-10, but not IL-17, were also detectable in the spleens of cytokine reporter mice. They provided help for IgG production in vivo, and expanded systemically in pristane-induced lupus-like disease. In SLE patients, CD4+CCR6+IL-7R+T cells were associated with the presence of pathogenic anti-dsDNA (double-stranded DNA) antibodies, and provided spontaneous help for autoantibody production ex vivo. Strikingly, IL-10-producing CCR6+T cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margins of follicles. In conclusion, we identified a previously uncharacterized population of extrafollicular B helper T cells, which produced IL-10 and could play a prominent pathogenic role in SLE.
Subject(s)
B-Lymphocytes/immunology , Interleukin-10/immunology , Lupus Erythematosus, Systemic/immunology , Receptors, CCR6/immunology , T-Lymphocytes, Helper-Inducer/immunology , Adult , Animals , Antibody Formation , Child , Cytokines/immunology , Humans , Interleukin-10/biosynthesis , Interleukin-17/metabolism , Lupus Erythematosus, Systemic/metabolism , Mice , Mice, Inbred C57BL , Palatine Tonsil/cytology , Palatine Tonsil/immunology , Receptors, CCR6/biosynthesis , Th17 Cells/immunologyABSTRACT
All abdominoperineal resections for carcinoma of the rectum carried out 1963-1972 in two small community hospitals are reviewed. Seventy-six patients were found: males slightly outnumbered females; the average age was 61. There were 67 adenocarcinomas, 7 squamous cell carcinomas and one each of villous adenoma and carcinoid. Distribution of Dukes' classification was: A-20, B-26, C-21, D-9. In an average case the operative time was 3 hours, 25 minutes, 4 units of blood were used, and postoperative hospital stay was 30 days. Postoperative complications were recorded in over 50% of the patients with reoperation needed in 26% of all patients and delayed complications occurred in 41%. The operative mortality was 1.3%. Five year followup was possible in 40 of 43 patients; survival according to Dukes' classification was A-80%, B-53%, C-9% and D-25% with overall survival 45%.
