- Poster presentation
- Open Access
Chronic SIV infection induces differentiation and accumulation of cytotoxic CD16+ NK cells in lymph nodes followed by transmigration to the mucosae
© Li et al; licensee BioMed Central Ltd. 2012
- Published: 13 September 2012
- Natural Killer
- Natural Killer Cell
- Cytotoxic CD16
- Killing Assay
- Direct Killing
Natural killer (NK) cells inhibit lentiviral replication both directly and indirectly, but substantial evidence also indicates HIV/SIV can induce NK cell dysfunction. NK cells can be subdivided based on expression of CD56 and CD16. In blood, cytotoxic CD16+ NK cells are the dominant subpopulation, while cytokine-secreting CD56+ and double-negative (DN) NK cells are the primary NK cells found in lymph nodes (LN). Furthermore, CD56+ and DN NK are thought to be precursor populations, whereas CD16+ NK cells are terminally differentiated. The effects of HIV/SIV infection on NK cell distribution, trafficking, and development are unclear.
Macaque NK cells were isolated from blood, LN, and mucosal tissues of naive and chronically SIV-infected animals and then analyzed phenotypically by surface and intracellular flow cytometry, evaluated functionally by ICS and in a direct killing assay against MHC-devoid 721.221 cells. In situ analyses were performed by immunohistochemistry.
In peripheral blood of chronically infected animals, we found a specific expansion of CD16+ NK cells, coupled with high frequencies of cytotoxic perforin+ CD16+ NK cells in LN, where they are normally absent. Interestingly, classic LN-trafficking molecules, CD62L and CCR7, were downregulated to undetectable levels on blood and LN CD16+ NK cells, suggesting they did not migrate from extralymphoid tissues. Furthermore, the putative NK cell precursors, CD56+ and DN NK cells, exhibited increased proliferation and activation, providing a potential source of differentiated CD16+ NK cells. CD16+ NK cells in LN also upregulated the mucosa-trafficking marker, α4β7, correlating with increased frequencies of cytotoxic CD16+ NK cells in colorectal and jejunum tissues of infected animals.
Our data suggest a novel mechanism whereby lentivirus infection induces differentiation of cytotoxic CD16+ NK cells, which are normally absent in LN, to differentiate in situ and then transmigrate to the gut mucosa, the primary site of virus replication.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.