PMID- 18647857 OWN - NLM STAT- MEDLINE DCOM- 20090903 LR - 20090716 IS - 1468-2060 (Electronic) IS - 0003-4967 (Linking) VI - 68 IP - 8 DP - 2009 Aug TI - Regulatory IL4+CD8+ T cells in patients with ankylosing spondylitis and healthy controls. PG - 1345-51 LID - 10.1136/ard.2008.088120 [doi] AB - OBJECTIVES: Interleukin (IL)4+CD8+ regulatory T cells (Treg) obtained from peripheral blood mononuclear cells (PBMCs) from patients with ankylosing spondylitis (AS) by coculture with autologous dendritic cells (DC) have been previously described. In the present work, the proportions of IL4+CD8+ T cells in PB from patients with AS and controls are examined; in addition the conditions required for the generation of IL4+CD8+ Treg cells and their frequency in T cell lines from patients with AS and controls are investigated. METHODS: CD8+ T cells were either stimulated non-specifically ex vivo and intracellular cytokines examined, or cocultured with DC and other stimuli, for 2 weeks. The resulting lines were analysed for cytokine expression. Clones derived from these lines were tested for regulatory function. RESULTS: PBMCs from patients with AS and from human leukocyte antigen (HLA)-B27+ healthy controls contained a higher frequency of IL4+CD8+ T cells than those from HLA-B27- controls. Likewise, CD8+ T cell lines obtained by coculture with DC contained a higher ratio of IL4+ to interferon (IFN)gamma+ cells when obtained from patients with AS or HLA-B27+ controls. T cell clones obtained from these lines showed regulatory activity. Outgrowth of IL4+ CD8+ T cells required contact with DC, but not maturation with lipopolysaccharide (LPS); allogeneic DC were also effective. Coculture with lymphoblastoid cells, or anti-CD3/CD28 microbeads, produced only expansion of IFN gamma-producing CD8+ T cells. CONCLUSIONS: The higher proportion of CD8+ cells which can produce IL4 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 IL4+CD8+ T cells may play a role in pathogenesis of spondyloarthritis. FAU - Zhang, L AU - Zhang L AD - Department of Rheumatology and Immunology, Changzheng Hospital, Shanghai, China. FAU - Jarvis, L B AU - Jarvis LB FAU - Baek, H-J AU - Baek HJ FAU - Gaston, J S Hill AU - Gaston JS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080722 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (HLA-B27 Antigen) RN - 207137-56-2 (Interleukin-4) SB - IM MH - Adult MH - Cell Communication/immunology MH - Cell Line MH - Coculture Techniques MH - Dendritic Cells/immunology MH - Female MH - HLA-B27 Antigen/blood MH - Humans MH - Interleukin-4/*biosynthesis MH - Lymphocyte Activation/immunology MH - Male MH - Middle Aged MH - Spondylitis, Ankylosing/*immunology MH - T-Lymphocyte Subsets/*immunology MH - T-Lymphocytes, Regulatory/*immunology EDAT- 2008/07/24 09:00 MHDA- 2009/09/04 06:00 CRDT- 2008/07/24 09:00 PHST- 2008/07/24 09:00 [pubmed] PHST- 2009/09/04 06:00 [medline] PHST- 2008/07/24 09:00 [entrez] AID - ard.2008.088120 [pii] AID - 10.1136/ard.2008.088120 [doi] PST - ppublish SO - Ann Rheum Dis. 2009 Aug;68(8):1345-51. doi: 10.1136/ard.2008.088120. Epub 2008 Jul 22.