The differential impact of natural killer (NK) cell education via KIR2DL3 and KIR3DL1 on CCL4 secretion in the context of in-vitro HIV infection
Autor: | Irene Lisovsky, B. Lebouchẻ, Gamze Isitman, Jean-Pierre Routy, Nicole F. Bernard, Julie Bruneau, Alexandra Tremblay-McLean, Rujun Song, S. DaFonseca |
---|---|
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Genotype Immunology Cell Context (language use) HIV Infections Human leukocyte antigen HLA-C Antigens Biology Lymphocyte Activation Flow cytometry 03 medical and health sciences 0302 clinical medicine Interferon HLA Antigens medicine Immunology and Allergy Humans Receptor Chemokine CCL4 Cells Cultured medicine.diagnostic_test Homozygote Receptors KIR3DL1 Original Articles In vitro 3. Good health Killer Cells Natural 030104 developmental biology medicine.anatomical_structure Receptors KIR2DL3 HIV-1 Leukocytes Mononuclear KIR3DL1 030215 immunology medicine.drug |
Zdroj: | Clinical and experimental immunology. 186(3) |
ISSN: | 1365-2249 |
Popis: | Summary Carriage of certain inhibitory natural killer (NK) cell receptor (iNKR)/HLA ligand pairs is associated with protection from infection and slow time to AIDS implicating NK cells in HIV control. NK cells acquire functional potential through education, which requires the engagement of iNKRs by their human leucocyte antigen (HLA) ligands. HIV infection down-regulates cell surface HLA-A/B, but not HLA-C/E. We investigated how NK cell populations expressing combinations of the iNKRs NKG2A, KIR2DL3 (2DL3) and KIR3DL1 (3DL1) responded to autologous HIV infected CD4 (iCD4) cells. Purified NK cells from HIV-uninfected individuals were stimulated with autologous HIV iCD4 or uninfected CD4 T cells. Using flow cytometry we gated on each of the 8 NKG2A+/–2DL3+/–3DL1+/- populations and analysed all possible combinations of interferon (IFN)-γ, CCL4 and CD107a functional subsets responding to iCD4 cells. Infected CD4 cells induced differential frequencies of NKG2A+/–2DL3+/–3DL1+/– populations with total IFN-γ+, CCL4+ and CD107a+ functional profiles. 2DL3+NKG2A+ NK cells had a higher frequency of responses to iCD4 than other populations studied. A higher frequency of 2DL3+ NK cells responded to iCD4 from individuals that were not HLA-C1 homozygotes. These results show that 2DL3+ NK cells are mediators of HIV-specific responses. Furthermore, responses of NK cell populations to iCD4 are influenced not only by NK cell education through specific KIR/HLA pairs, but also by differential HIV-mediated changes in HLA expression. |
Databáze: | OpenAIRE |
Externí odkaz: | |
Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |