Characterisation of mucosal lymphoid aggregates in ulcerative colitis: immune cell phenotype and TcR-gammadelta expression.
OBJECTIVE
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(+)CD28(-) alphabeta 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, gammadelta T cells (11 (7)%) and alpha(E)beta(7)(+) cells (26 (13)%). The gammadelta T cells used Vdelta1 and were CD4(-)CD8(-). Immunoelectron microscopy analysis demonstrated TcR-gammadelta internalisation and surface downregulation, indicating that the gammadelta 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 gammadelta 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. gammadelta T cells in the aggregates may be characteristic of UC.
Yeung
M M
MM
Department of Immunology, Umeå University, Sweden.
Melgar
S
S
Baranov
V
V
Oberg
A
A
Danielsson
A
A
Hammarström
S
S
Hammarström
M L
ML
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000473:pathology; D020566:Dendritic Cells, Follicular / Q000166:cytology; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D019676:Genes, T-Cell Receptor delta / Q000235:genetics; D019254:Genes, bcl-2; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D016692:Receptors, Antigen, T-Cell, gamma-delta; D016201:Receptors, Lymphocyte Homing