THE ROLE OF CD8(-CELLS IN THE FORMATION OF GERMINAL-CENTERS IN RHEUMATOID SYNOVITIS() CD40L(+) T)

In rheumatoid synovitis, lymphocytes can be arranged in follicular str uctures resembling secondary lymphoid follicles. To understand the org anizing principles of this ectopic lymphoid tissue, the cellular compo nents contributing to synovial follicles mere examined, In 9 of 24 syn ovial tissue biopsies, lymphoid aggregates were found consisting of CD 4(+) T cells and CD20(+) B cells. In four of the nine patients, the fo llicular centers were occupied by CD23(+) CD21(+) cellular networks re presenting follicular dendritic cells involved in germinal center reac tions. 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 i n the regulation of the synovial microarchitecture, cell populations c ontributing to the follicles were quantified by digital image analysis of immunostained tissue and by flow cytometry of tissue-derived lymph ocytes, Proportions of CD4(+), CD20(+), and CD68(+) cell subsets were surprisingly invariant, irrespective of the presence or absence of CD2 3(+) follicular dendritic cells. Instead, tissue biopsies with CD23(+) germinal center-like regions could be distinguished from those with C D23(-) T cell-B cell aggregates by a fourfold increase in the frequenc y of tissue-infiltrating CD8(+) T cells, a fraction of which expressed CD40 ligand (CD40L), The data suggest a previously unsuspected role o f CD8(+) lymphocytes in modulating germinal center formation and raise the possibility that CD8(+) CD40L(+) T cells are involved in aggravat ing pathologic immune responses in rheumatoid synovitis.