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Evaluation of the age-dependent role of natural killer t cells in gammaherpesvirus infection

University of British Columbia

Epstein-Barr virus (EBV), a human gammaherpesviruses, demonstrates age dependent- pathogenesis. EBV infection in young children is usually asymptomatic, whereas primary EBV infection later in life frequently results in the development of infectious mononucleosis (IM) due to uncontrolled expansion of CD8⁺ T lymphocytes. Natural killer (NK) T cells are innate T lymphocytes that respond to various pathogens through recognition of lipid antigens presented by CD1d receptors. Previous findings suggested that NKT cells have cytotoxic effects on EBV-infected cell lines. Furthermore, infection with other herpesviruses such as Kaposi’s sarcoma-associated herpesvirus (KSHV) and herpes simplex virus (HSV) can modulate the host immune response to evade NKT cells. To explain the age dependence of EBV pathogenesis, we hypothesized that there is an early window of opportunity to control gammaherpesvirus infection by invariant NKT cells. To test our hypothesis, we infected both neonatal and adult wild type and CD1d knock out (CD1d KO) C57BL/6 mice with murine gammaherpesvirus 68 (MHV-68). Our readout was the quantification of virus copy number by qPCR from genomic DNA extracted from lung and spleen. We report that there was no significant difference in symptoms and viral load between adult and young C57BL/6 and CD1dKO mice. We conclude that NKT cells do not have a major role in the control of gammaherpesvirus infection. The inability of NKT cells to control MHV-68 infection may be due to virus-mediated downregulation of CD1d expression on B cells.

Text

2016-01-15

Attribution-NonCommercial-NoDerivs 2.5 Canada

http://hdl.handle.net/2429/56494

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/2.5/ca/