Journal
JCI INSIGHT
Volume 7, Issue 8, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.155601
Keywords
-
Categories
Funding
- Emory CFAR (Erase AIDS grant)
- YNPRC Division of Research Resources
- NIH [AIDS-R03, R01 HD095741, R01AI148377, U19 AI109633, R01 AI148080]
- Emory University CFAR grant [P30 AI050409]
- NIH Office of Research Infrastructure Programs (ORIP) grants [P51 OD011132, U42 OD011023, R24 OD010947]
- YNPRC Division of Pathology
Ask authors/readers for more resources
The study found that follicular homing NK cells may play an important role in immune control of chronic SHIV infection, with implications for HIV cure strategies.
The persistence of virally infected cells as reservoirs despite effective antiretroviral therapy is a major barrier to an HIV/SIV cure. These reservoirs are predominately contained within cells present in the B cell follicles (BCFs) of secondary lymphoid tissues, a site that is characteristically difficult for most cytolytic antiviral effector cells to penetrate. Here, we identified a population of NK cells in macaque lymph nodes that expressed BCF-homing receptor CXCR5 and accumulated within BCFs during chronic SHIV infection. These CXCR5(+) follicular NK cells exhibited an activated phenotype coupled with heightened effector functions and a unique transcriptome characterized by elevated expression of cytolytic mediators (e.g., perforin and granzymes, LAMP-1). CXCR5(+) NK cells exhibited high expression of Fc gamma RIIa and Fc gamma RIIIa, suggesting a potential for elevated antibody-dependent effector functionality. Consistently, accumulation of CXCR5(+) NK cells showed a strong inverse association with plasma viral load and the frequency of germinal center follicular Th cells that comprise a significant fraction of the viral reservoir. Moreover, CXCR5(+) NK cells showed increased expression of transcripts associated with IL-12 and IL-15 signaling compared with the CXCR5-subset. Indeed, in vitro treatment with IL-12 and IL-15 enhanced the proliferation of CXCR5(+) granzyme B+ NK cells. Our findings suggest that follicular homing NK cells might be important in immune control of chronic SHIV infection, and this may have important implications for HIV cure strategies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available