Effects of Increased Inflammation on Antiviral CD8+ T Cell Responses in Mice Overexpressing the Human-Cysteinyl Leukotriene 2 Receptor (hCysLT2R)

Abstract

Inflammation plays a vital role in promoting naïve cytotoxic T lymphocyte (CD8+ T cell) differentiation. Infection with lymphocytic choriomeningitis virus (LCMV) elicits a robust CD8+ T cell response in the mouse. Cysteinyl leukotrienes (CysLTs) are involved in inflammation and the transgenic mice (TG) overexpressing the cysteinyl leukotriene 2 receptor (hCysLT2R) exhibit increased expression of pro-inflammatory transcription factors after stimulation. Here, we investigate how increased inflammation can affect the activation of CD8+ T cells during viral infection in TG mice with different doses (low vs. high) of LCMV. Pro-inflammatory cytokine levels in the serum of TG mice were increased after infection with low or high viral doses. The data also showed the accumulation of a higher number of effector CD8+ T cells in TG mice compared to WT mice on day 12 p.i with low or high viral doses in peripheral tissues. Analysis of memory CD8+ T cells 40 days p.i indicated increased accumulation of central memory CD8+ T cells in peripheral tissue (lungs) of TG mice compared to WT mice, irrespective of the viral doses. However, for the lymphoid tissue (spleen) no difference in memory CD8+ T cell formation was recorded during infection with a low viral dose, but a lower central memory CD8+ T cell number was recorded in the spleen of TG mice compared to WT mice with higher viral doses. From the results obtained, it can be concluded that increased inflammation can cause a stronger migration of effector and memory CD8+ T cells to peripheral tissue irrespective of the viral dose. On the other hand, increased inflammation resulted in decreased central memory CD8+ T cell formation in lymphoid tissue (spleen) during a high viral dose infection, but not during infection with a low viral dose. Therefore, using mice expressing the hCysLT2R has enabled us to examine how increased inflammation during viral infections can impact the activation of T cells and how this influences their memory phenotype formation.