NK markers are expressed on a high percentage of virus-specific CD8⁺ and CD4⁺ T cells

NK cells have been phenotypically defined by the expression of specific markers such as NK1.1, DX5, and asialo-GM1 (ASGM1). In addition to NK cells, a small population of CD3⁺ T cells has been shown to express these markers, and a unique subpopulation of NK1.1⁺ CD3⁺ T cells that expresses an invariant TCR has been named 'NKT cells.' Here, we describe NK marker expression on a broad spectrum of MHC class I- and MHC class II-restricted T cells that are induced after acute viral infection. From 5 to > 500 days post lymphocytic choriomeningitis virus (LCMV) infection, more than 90% of virus- specific CD8⁺ and CD4⁺ T cells coexpress one or more of these three prototypical NK markers. Furthermore, in vivo depletion of NK cells with anti-ASGM1 Ab resulted in the removal of 90% of virus-specific CD8⁺ T cells and 50-80% of virus-specific CD4⁺ T cells. This indicates that studies using in vivo depletion to determine the role of NK cells in immune defense could potentially be misinterpreted because of the unintended depletion of Ag- specific T cells. These results demonstrate that NK Ags are widely expressed on the majority of virus-specific T cells and indicate that the NK and T cell lineages may not be as distinct as previously believed. Moreover, the current nomenclature defining NKT cells will require comprehensive modification to include Ag-specific CD8⁺ and CD4⁺ T cells that express prototypical NK Ags.