期刊
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
卷 63, 期 2, 页码 161-167出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAI.0b013e318285cf13
关键词
Tim-3; HIV; innate immunity; inflammation
资金
- CTN/OHTN
- OHTN Junior Investigator Development Award
- Canada Research Chair in Molecular Parasitology
- CIHR [MOP-13721, 115160, CI1-103128]
Background: The Tim-3 receptor has been implicated as a negative regulator of adaptive immune responses and has been linked to T-cell dysfunction in chronic viral infections, such as HIV. Blocking Tim-3 has been proposed as a potential therapeutic intervention in HIV infection. However, a more detailed characterization of Tim-3 expression in the presence of HIV is required before such strategies can be considered. Methods: In this study, we investigate Tim-3 expression on innate immune cell subsets in chronic HIV-infected individuals pretherapy and posttherapy. Results: We report that, pretherapy, HIV infection is associated with elevated levels of Tim-3 on resting innate lymphocytes (NK, NKT, and gamma delta T cells), but not resting monocytes. In the absence of HIV infection, stimulation with an inflammatory stimulus resulted in decreased Tim-3 on monocytes and increased Tim-3 on NK, NKT, and gamma delta T cells. However, innate cells from HIV-infected donors were significantly less responsive to stimulation. Six months of combination antiretroviral therapy (cART) restored Tim-3 levels on resting NK cells but not NKT or gamma delta T cells. The responses of all subsets to inflammatory stimuli were restored to some extent with cART but only reached HIV-negative control levels in monocytes and NK cells. Discussion: These results demonstrate that, during HIV infection, Tim-3 expression on innate cells is dysregulated and that this dysregulation is only partially restored after 6 months of cART. Our findings suggest that Tim-3 is differentially regulated on innate immune effector cells, and have direct implications for strategies designed to block Tim-3-ligand interactions.
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