Abstract
The role of Ly49+CD8 T-cells in the immune system is not clear. Previously, several papers suggested Ly49+CD8 T-cells as immunosuppressors, while multiple studies also suggested their role as potent participants of the immune response. The mechanism of Ly49 expression on CD8 T-cells is also not clear. We investigated phenotype, functions, and regulation of Ly49 expression on murine CD8 T-cells in both normal state and during LCMV infection. CD8 T-cells express different Ly49 receptors compared with NK-cells. In intact mice, Ly49+CD8 T-cells have a phenotype similar to resting central memory CD8 T-cells and do not show impaired proliferation and cytokine production. Conventional CD8 T-cells upregulate Ly49 receptors during TCR-induced stimulation, and IL-2, as well as IL-15, affect it. At the same time, Ly49+CD8 T-cells change the Ly49 expression profile dramatically upon re-stimulation downregulating inhibitory and upregulating activating Ly49 receptors. We observed the expression of Ly49 receptors on the virus-specific CD8 T-cells during LCMV infection, especially marked in the early stages, and participation of Ly49+CD8 T-cells in the anti-viral response. Thus, CD8 T-cells acquire Ly49 receptors during the T-cell activation and show dynamic regulation of Ly49 receptors during stimulation.
Highlights
memory phenotype CD8 T-cells (CD8) T-cells express MHC class I-specific NK-cell receptors (NKRs) belonging to the killer immunoglobulin-like family of receptors (KIRs) in humans and lectin-like receptors of the Ly49 receptor family in mice [1, 2]
We demonstrate the positive effect of Ly49+CD8 T-cells from lymphocytic choriomeningitis virus (LCMV)-immune mice on the antiviral response upon adoptive transfer
Depending on the site analyzed (Figure 1A), the amount of Ly49+CD8 T-cells among total CD8 T-cells varies from 4 to 8% in lymph nodes and spleen with only a slightly higher percentage in the liver and significant enrichment within the bone marrow compared with the other organs analyzed (Figure 1A)
Summary
CD8 T-cells express MHC class I-specific NK-cell receptors (NKRs) belonging to the killer immunoglobulin-like family of receptors (KIRs) in humans and lectin-like receptors of the Ly49 receptor family in mice [1, 2]. Generation and Functions of Ly49+ CD8 T-Cells chronic infections, such as viral infections (HIV, HCV, CMV), parasitic infections (Trypanosoma cruzi), or cancer [3,4,5,6,7,8,9]. These cells show reduced effector properties, but they have survival benefits and play a role in the disease control in case of functional interactions of expressed KIRs with the corresponding MHC class I ligands [6,7,8]. Several studies report these cells to have efficient immunosuppressive capacities [11, 12], while other studies demonstrate the participation of Ly49+CD8 T-cells in the immune response and the ability to lyse virus-infected target cells [13,14,15]
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