Objectives: We previously described IL-4+CD8+ regulatory T cells (Treg) obtained from AS patients' PBMC by co-culture with autologous dendritic cells (DC). We now examine the proportions of IL-4+CD8+ T cells in PB of AS patients and controls; in addition we investigate conditions required for the generation of IL-4+CD8+ Treg and their frequency in T cell lines from AS patients and controls.
Methods: CD8+ T cells were either stimulated non-specifically ex vivo and intracellular cytokines examined, or co-cultured with DC, and other stimuli, for two weeks and the resulting lines analysed for cytokine expression. Clones derived from these lines were tested for regulatory function.
Results: PBMC from AS patients, and from HLA-B27+ healthy controls, contained a higher frequency of IL-4+CD8+ T cells than those from HLA-B27- controls. Likewise, CD8+ T cell lines obtained by co-culture with DC contained a higher ratio of IL-4+ to IFNγ+ cells when obtained from AS patients or HLA-B27+ controls. T cell clones obtained from these lines showed regulatory activity. Outgrowth of IL-4+ CD8+ T cells required contact with DC, but not maturation with LPS; allogeneic DC were also effective. Co-culture with lymphoblastoid cells, or anti-CD3/CD28 microbeads, produced only expansion of IFNγ-producing CD8+ T cells.
Conclusions: The higher proportion of CD8+ cells which can produce IL-4 in PB and in expanded CD8+ T cell lines, suggests an altered pattern of CD8+ T cell differentiation in AS, and in HLA-B27+ healthy individuals. This predisposition to generate IL-4+CD8+ T cells may play a role in pathogenesis of spondyloarthritis.
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