Functional modulation of expanded CD8+ synovial fluid T cells by NK cell receptor expression in HLA-B27-associated reactive arthritis.
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.
Dulphy
Nicolas
N
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.
Rabian
Claire
C
Douay
Corinne
C
Flinois
Odile
O
Laoussadi
Saddek
S
Kuipers
Jens
J
Tamouza
Ryad
R
Charron
Dominique
D
Toubert
Antoine
A
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D016918:Arthritis, Reactive / Q000276:immunology*; D017252:CD3 Complex / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D015796:HLA-B27 Antigen / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000032:analysis; D051920:NK Cell Lectin-Like Receptor Subfamily D; D000091402:Prohibitins; D011971:Receptors, Immunologic / Q000378:metabolism*; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054343:Receptors, KIR2DL2; D054341:Receptors, KIR3DL1; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017252:CD3 Complex; D016827:CD8 Antigens; D015796:HLA-B27 Antigen; C515077:KIR2DL2 protein, human; C515083:KIR3DL1 protein, human; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; C000717331:PHB2 protein, human; D000091402:Prohibitins; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054343:Receptors, KIR2DL2; D054341:Receptors, KIR3DL1