Skip to main content

Volume 9 Supplement 2

AIDS Vaccine 2012

Chronic SIV infection induces differentiation and accumulation of cytotoxic CD16+ NK cells in lymph nodes followed by transmigration to the mucosae

Background

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.

Methods

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.

Results

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.

Conclusion

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.

Author information

Affiliations

Authors

Corresponding author

Correspondence to R Reeves.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Li, H., Evans, T., Gillis, J. et al. Chronic SIV infection induces differentiation and accumulation of cytotoxic CD16+ NK cells in lymph nodes followed by transmigration to the mucosae. Retrovirology 9, P179 (2012). https://doi.org/10.1186/1742-4690-9-S2-P179

Download citation

Keywords

  • Natural Killer
  • Natural Killer Cell
  • Cytotoxic CD16
  • Killing Assay
  • Direct Killing