Comparison of abacavir-specific effector and proliferating functions of CD8 T cells in abacavir-treated HIV-1 patients
| Autor: | Poonam Dharmani-Khan, Stuti Patel, Rehan M. Faridi, Faisal Khan, John Gill, Noureddine Berka |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Anti-HIV Agents
medicine.medical_treatment Immunology HIV Infections Biology CD8-Positive T-Lymphocytes Microbiology Peripheral blood mononuclear cell Drug Hypersensitivity 03 medical and health sciences Interferon-gamma Immune system Abacavir Virology medicine Cytotoxic T cell Humans 030304 developmental biology 0303 health sciences 030306 microbiology Degranulation Immunotherapy Dideoxynucleosides Cytokine HLA-B Antigens HIV-1 Leukocytes Mononuclear Cytokines CD8 medicine.drug |
| Zdroj: | Microbiology and immunologyREFERENCES. 64(3) |
| ISSN: | 1348-0421 |
| Popis: | Susceptibility to abacavir hypersensitivity (ABH) in HIV-1-positive patients is strongly linked to the carriage of HLA-B*57:01 and the potential mechanism includes drug-specific activation of cytokine producing CD8 T cells exclusively in individuals carrying HLA-B*57:01. Here, we report a detailed characterization of abacavir-induced functional response of CD8 T cells in HLA-B*57:01pos individuals. Peripheral blood mononuclear cells (PBMNCs) from HLA-B*57:01pos ABHpos and HLA-B*57:01neg ABHneg individuals were stimulated with abacavir. Multicolor flow cytometry was performed to assess the cytokine (IFNγ) production and degranulation (CD107a expression) after 6-18 hr culture and to enumerate proliferating CD4/CD8 T cells by culturing carboxyfluorescein diacetate succinimidyl ester-loaded PBMNCs for 7 days. CD8 T cells from HLA-B*57:01pos ABHpos individuals were multifunctional: proliferating, IFNγ producing, degranulating (CD107apos ), and both degranulating and IFNγ producing (CD107apos IFNγpos ). Degranulating CD8 T cells in general and both degranulating and IFNγ producing CD8 T cells in particular dominated abacavir-specific immune response. All functional responses were partially blocked by addition of HLA-B*57:01-reactive Bw4 mAb, but not by non-HLA-B*57:01-reactive Bw6 mAb. In conclusion, the study demonstrates that abacavir-specific CD8 T-cell-restricted immune response in HLA-B*57:01pos ABHpos HIV-1 patients has multiple effector and proliferating functions, where the primary effector response appears to be the release of cytolytic granules. The findings have implications for immunotherapy of HLA-related drug hypersensitivities. |
| Databáze: | OpenAIRE |
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