ABSTRACT
The interaction between clonally distributed inhibitory receptors and their activating counterparts on NK cells and HLA class I molecules defines NK cell functions, but the role of HLA class I ligands in the acquisition of their receptors during NK development is still unclear. Although some studies demonstrated that HLA-C affects the expression of killer Ig-like receptors (KIR), other studies showed that NK cells acquire their KIR repertoire in a stochastic manner. Only when infected with human CMV is an expansion of self-specific KIR(+) NKG2C(+) NK cells detected. To gain more insight into this question, we compared the coexpression of different KIR molecules, NKG2A, CD8, and CD57, on NK cells in healthy donors and seven patients with deficient HLA class I expression due to mutations in one of the TAP genes. Our results show a correlation between the presence/absence of HLA class I molecules and the coexpression of their receptors. In an HLA class I low-expression context, an increase in KIR molecules' coexpression is detected on the NKG2A(+) CD8(+) subset. In functional assays, hyporesponsiveness was observed for TAP-deficient NK cells derived from four patients. In contrast, NK cells from patient five were functional, whereas CD107a(+) and IFN-γ(+) CD56(dim) NK cells presented a different pattern of HLA class I receptors compared with healthy donors. Taken together, our results provide strong evidence for the role of HLA class I molecules in NK cell maturation and KIR repertoire acquisition.
Subject(s)
Cell Differentiation/immunology , Histocompatibility Antigens Class I/immunology , Killer Cells, Natural/immunology , Receptors, KIR/immunology , ATP Binding Cassette Transporter, Subfamily B, Member 2 , ATP-Binding Cassette Transporters/deficiency , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/immunology , Adult , CD56 Antigen/immunology , CD56 Antigen/metabolism , CD57 Antigens/immunology , CD57 Antigens/metabolism , CD8 Antigens/immunology , CD8 Antigens/metabolism , Cell Differentiation/genetics , Female , Flow Cytometry , Genotype , HLA-A Antigens/genetics , HLA-A Antigens/immunology , HLA-A Antigens/metabolism , HLA-B Antigens/genetics , HLA-B Antigens/immunology , HLA-B Antigens/metabolism , HLA-C Antigens/genetics , HLA-C Antigens/immunology , HLA-C Antigens/metabolism , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/metabolism , Humans , Interferon-gamma/immunology , Interferon-gamma/metabolism , Killer Cells, Natural/metabolism , Lysosomal-Associated Membrane Protein 1/immunology , Lysosomal-Associated Membrane Protein 1/metabolism , Male , Middle Aged , Mutation , NK Cell Lectin-Like Receptor Subfamily C/immunology , NK Cell Lectin-Like Receptor Subfamily C/metabolism , Receptors, KIR/genetics , Receptors, KIR/metabolismSubject(s)
Biomarkers, Tumor/metabolism , Lymphoma , MicroRNAs/metabolism , RNA, Neoplasm/metabolism , Retinal Neoplasms , Vitreous Body , Adult , Aged , Female , Humans , Lymphoma/diagnosis , Lymphoma/metabolism , Lymphoma/pathology , Male , Middle Aged , Retinal Neoplasms/diagnosis , Retinal Neoplasms/metabolism , Retinal Neoplasms/pathology , Vitreous Body/metabolism , Vitreous Body/pathologySubject(s)
Aldehyde Reductase , Diabetic Retinopathy , Lipase , Humans , Diabetic Retinopathy/genetics , Diabetic Retinopathy/epidemiology , Aldehyde Reductase/genetics , Lipase/genetics , Male , Prospective Studies , Female , France/epidemiology , Middle Aged , Aged , Polymorphism, Single NucleotideABSTRACT
PURPOSE: To demonstrate the importance of collaboration between ophthalmologists and internists. DESIGN: Cryoglobulinemia is a systemic vascularite. Ophthalmologic complications are rare and not well known. Purtscher-like retinopathy may occur in this context. CASE REPORT: We report the case of a patient who presented a severe visual loss in the course of a hepatitis C. The ophthalmic examination shows a both ischemic and hemorrhagic bilateral retinopathy called Purtscher-like retinopathy. Cryoglobulinemia complicating a hepatitis C was discovered in our patient. CONCLUSIONS: This case illustrates a cryoglobulinemia complicating by a Purtscher-like retinopathy. The diagnosis has been possible thanks to collaboration between ophthalmologists and internists. We propose a few hypotheses to explain retinopathy pathogeny.