International Immunology, Vol. 14, No. 5, pp. 471-479,
May 2002
© 2002 Japanese Society for Immunology
Functional modulation of expanded CD8+ synovial fluid T cells by NK cell receptor expression in HLA-B27-associated reactive arthritis
1 Laboratoire d‘Immunologie et d‘Histocompatibilité, INSERM U396, Centre G. Hayem, Université Paris VII, Institut Universitaire d’Hématologie, Hôpital Saint-Louis, Avenue C. Vellefaux, 75475 Paris Cedex 10, France 2 Service de Rhumatologie A, Hôpital Cochin, 75679 Paris Cedex 14, France 3 Division of Rheumatology, Medical School, 30625 Hannover, Germany
Correspondence to: A. Toubert; E-mail: toubert{at}histo.chu-stlouis.fr
Transmitting editor: T. Sasazuki
The aim of this study was to determine whether NK cell receptor (NKR) expression could modulate cytotoxicity of oligoclonal CD8+ T cells present in the synovial fluid (SF) of HLA-B27-reactive arthritis (ReA) patients, especially in a TCRBV1 population shared among different patients and cytotoxic toward HLA-B27. A CD8+ T cell line, two TCRBV1 lines and clones were isolated from the SF of an HLA-B27+ ReA patient, and tested with mAb specific for Ig-like (KIR2DL1, KIR2DL2, KIR3DL1 and ILT2) and CD94 C-type lectin NKR. Transcripts for NKG2 subunits (NKG2A–2E) associated with CD94 were also evaluated. Function was tested in a 51Cr-release cytotoxic assay. We found stable but distinct levels of CD94/NKG2 complexes at the surface of T cell lines and clones. Different NKG2 members could be associated with CD94, either inhibitory (NKG2A/B) or activating (NKG2C). The inhibitory ILT2 receptor could also be differently expressed, but other Ig-like NKR were negative. Functionally, one TCRBV1 line and clones with a high CD94/NKG2A expression did not lyse B27+ targets. Another TCRBV1 line with the same TCRBV1 rearrangement had a low expression of CD94/NKG2A, but expressed NKG2C transcripts and was cytotoxic toward HLA-B27. HLA-B27 is a ligand for ILT2 and we observed an inhibitory effect of ILT2 engagement on B*2705 targets in blockade experiments. Altogether, these data indicate a high degree of heterogeneity in the expression of NKR by intrasynovial CD8+ T cells which could modulate their cytotoxicity and play a role in the control of this HLA class I-associated autoimmune disease.
Keywords: autoimmunity, MHC, oligoclonal T cell expansions, spondyloarthropathies
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