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Characterisation of mucosal lymphoid aggregates in ulcerative colitis: immune cell phenotype and TcR-γδ expression
  1. M M-W Yeunga,
  2. S Melgara,
  3. V Baranova,
  4. Å Öbergb,
  5. Å Danielssonc,
  6. S Hammarströma,
  7. M-L Hammarströma
  1. aDepartment of Immunology, Umeå University, Umeå, Sweden, bDepartment of Surgery, Umeå University, Umeå, Sweden, cDepartment of Medicine, Section for Gastroenterology, Umeå University, Umeå, Sweden
  1. Dr M-L Hammarström, Department of Immunology, Umeå University, S-901 85 Umeå, Sweden. Email:Marie-Louise.Hammarstrom{at}climi.umu.se.

Abstract

BACKGROUND AND AIMS A histopathological feature considered indicative of ulcerative colitis (UC) is the so-called basal lymphoid aggregates. Their relevance in the pathogenesis of UC is, however, unknown. We have performed a comprehensive analysis of the immune cells in these aggregates most likely corresponding to the lymphoid follicular hyperplasia also described in other colitides.

METHODS Resection specimens of UC and normal colon were analysed by immunomorphometry, immunoflow cytometry, and immunoelectron microscopy, using a large panel of monoclonal antibodies.

RESULTS (1) In all cases of UC, colonic lamina propria contained numerous basal aggregates composed of lymphocytes, follicular dendritic cells, and CD80/B7.1 positive dendritic cells. (2) CD4+CD28αβ T cells and B cells were the dominant cell types in the aggregates. (3) The aggregates contained a large fraction of cells that are normally associated with the epithelium: that is, γδ T cells (11 (7)%) and αEβ7 +cells (26 (13)%). The γδ T cells used Vδ1 and were CD4CD8. Immunoelectron microscopy analysis demonstrated TcR-γδ internalisation and surface downregulation, indicating that the γδ T cells were activated and engaged in the disease process. (4) One third of cells in the aggregates expressed the antiapoptotic protein bcl-2.

CONCLUSIONS Basal lymphoid aggregates in UC colon are a consequence of anomalous lymphoid follicular hyperplasia, characterised by abnormal follicular architecture and unusual cell immunophenotypes. The aggregates increase in size with severity of disease, and contain large numbers of apoptosis resistant cells and activated mucosal γδ T cells. The latter probably colonise the aggregates as an immunoregulatory response to stressed lymphocytes or as a substitute for defective T helper cells in B cell activation. γδ T cells in the aggregates may be characteristic of UC.

  • basal lymphoid aggregates
  • ulcerative colitis
  • T cell receptor γδ
  • immunomorphology
  • Abbreviations used in this paper

    UC
    ulcerative colitis
    Ig
    immunoglobulin
    IBD
    inflammatory bowel disease
    TcR
    T cell receptor
    MHC
    major histocompatibility complex
    IL
    interleukin
    mAb
    monoclonal antibody
    PBS
    phosphate buffered saline
    BSA
    bovine serum albumin
    FDC
    follicular dendritic cells
    IEL
    intraepithelial lymphocytes
    LPL
    lamina propria leucocytes
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  • Abbreviations used in this paper

    UC
    ulcerative colitis
    Ig
    immunoglobulin
    IBD
    inflammatory bowel disease
    TcR
    T cell receptor
    MHC
    major histocompatibility complex
    IL
    interleukin
    mAb
    monoclonal antibody
    PBS
    phosphate buffered saline
    BSA
    bovine serum albumin
    FDC
    follicular dendritic cells
    IEL
    intraepithelial lymphocytes
    LPL
    lamina propria leucocytes
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