Toll‐Like Receptor and Cytokine Expression Patterns of CD56+T Cells Are Similar to Natural Killer Cells in Response to Infection with Venezuelan Equine Encephalitis Virus Replicons

Using the natural killer (NK) cell-surface marker CD56 to study NK T cells in peripheral blood, we found that their frequency in mononuclear cells among healthy individuals was 1%-20% (average, 7.3%) and sporadically increased 4-5-fold within individuals over the course of 8 months. Infection of mononuclear cells in vitro with Venezuelan equine encephalitis virus replicon particles (VRPs) resulted in a significant increase in CD56(+) T cells and in the expression of interferon-alpha, tumor necrosis factor (TNF)-alpha, and interferon-gamma by CD56(+) but not CD56(-) T cells. NK and CD56(+) T cells expressed higher levels of Toll-like receptor (TLR)-3 and TLR4 after infection with VRPs, whereas only NK cells expressed inducible TNF-alpha and TLR2. Most of these effects were duplicated by activating mononuclear cells with double-stranded RNA. These expression patterns indicate that T cells coexpressing NK markers respond like NK cells to viral infection or double-stranded RNA, potentially fulfilling innate and adaptive immune functions.