Functional modulation of expanded CD8+ synovial fluid T cells by NK cell receptor expression in HLA-B27-associated...

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.