Functional KIR2DS4 Allele Found Increased in Chronically Infected HCV Patients is Associated with its Expression on NK and Highly Differentiated CD8+ Cells.

ARIEL PODHORZER, N. PALADINO, G. THEILER J. PANDOLFI, S. PAZ, H.A. FAINBOIM, LEONARDO FAINBOIM

Cordoba

Congreso; LXI Reunion Anual de la Sociedad Argentina de Inmunología; 2013

Increased resolution of acute hepatitis C viral (HCV) infection was associated with the presence of inhibitory KIR genes showing the weaker interaction with MHC-1 ligands. In the present study we analyzed frequency of KIR genes, their expression in NK or NKT and modifications in their phenotype during progression of HCV infection. Patients: A cohort of 300 chronically monoinfected HCV patients were compared with 286 healthy controls (HC). Methods: All conditions to identify the presence or absence of each KIR gene, plus full length and deleted alleles forms of KIR2DS4 were previously documented (Maxwell et al, 2004). The expression of KIR genes was investigated by flow cytometry in a cohort of HCV patients, naïve of treatment using Mabs for KIR2DS4, CD4, CD8, CD3 and CD56. Results: The generic KIR typing of HCV patients showed no statistically differences with HCs; nevertheless the high resolution typing of KIR2DS4 revealed that the functional full length alleles were increased in HCV cohort (48%Vs 39%, p=0.03), in particular when analyzing their gene frequency: 39% Vs 30% in HCs; p=0.001,OR=1.5).Those patients who developed cirrhosis showed a stronger association with functional KIR2DS4 alleles with a gene frequency of 45% Vs 30% of HCs; p=0.0005,OR= 2.0). No differences were detected between non-cirrhotic patients and HC (p=0.15). We detected a high expression of the KIR2DS4 receptor in peripheral blood NKdim cells (40%±18) and in highly differentiated CD8+CD56+ cells (20%±14), that was even higher in the liver, because NKdim cells, and highly differentiated T cells represent around 60% of the liver mononuclear cells. Conclusions: Functional KIR2DS4 was found increased in chronically infected HCV patients, in particular those developing cirrhosis. The expression of their receptors in cells from innate and adaptative immune response support that a cross-talk between them could modulate T cell response during HCV infection.