The role of CD8+ CD40L+ T cells in the formation of germinal centers in rheumatoid synovitis

UG Wagner, PJ Kurtin, A Wahner… - The Journal of …, 1998 - journals.aai.org
UG Wagner, PJ Kurtin, A Wahner, M Brackertz, DJ Berry, JJ Goronzy, CM Weyand
The Journal of Immunology, 1998journals.aai.org
In rheumatoid synovitis, lymphocytes can be arranged in follicular structures resembling
secondary lymphoid follicles. To understand the organizing principles of this ectopic
lymphoid tissue, the cellular components contributing to synovial follicles were examined. In
9 of 24 synovial tissue biopsies, lymphoid aggregates were found consisting of CD4+ T cells
and CD20+ B cells. In four of the nine patients, the follicular centers were occupied by
CD23+ CD21+ cellular networks representing follicular dendritic cells involved in germinal …
Abstract
In rheumatoid synovitis, lymphocytes can be arranged in follicular structures resembling secondary lymphoid follicles. To understand the organizing principles of this ectopic lymphoid tissue, the cellular components contributing to synovial follicles were examined. In 9 of 24 synovial tissue biopsies, lymphoid aggregates were found consisting of CD4+ T cells and CD20+ B cells. In four of the nine patients, the follicular centers were occupied by CD23+ CD21+ cellular networks representing follicular dendritic cells involved in germinal center reactions. In five patients, CD23+ cells were absent from the centers of the aggregates, suggesting that fully developed germinal centers are generated in only a subset of patients. To identify factors involved in the regulation of the synovial microarchitecture, cell populations contributing to the follicles were quantified by digital image analysis of immunostained tissue and by flow cytometry of tissue-derived lymphocytes. Proportions of CD4+, CD20+, and CD68+ cell subsets were surprisingly invariant, irrespective of the presence or absence of CD23+ follicular dendritic cells. Instead, tissue biopsies with CD23+ germinal center-like regions could be distinguished from those with CD23− T cell-B cell aggregates by a fourfold increase in the frequency of tissue-infiltrating CD8+ T cells, a fraction of which expressed CD40 ligand (CD40L). The data suggest a previously unsuspected role of CD8+ lymphocytes in modulating germinal center formation and raise the possibility that CD8+ CD40L+ T cells are involved in aggravating pathologic immune responses in rheumatoid synovitis.
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