Reduced lymphocyte infiltration during cytomegalovirus brain infection of interleukin-10-deficient mice

Interleukin (IL)-10 deficiency results in highly elevated levels of interferon (IFN)-gamma, as well as the IFN-gamma-inducible chemokines CXCL9 and CXCL10 within murine cytomegalovirus (MCMV)-infected brains. To test the hypothesis that these elevated chemokine levels would result in enhanced brain infiltration, we compared immune cell infiltration in response to MCMV brain infection between wild-type and IL-10 knockout (KO) mice. Longitudinal analysis following adoptive transfer of cells from beta-actin-luciferase transgenic wild-type mice showed maximal brain infiltration by peripheral immune cells occurred at 5 days post infection. Although the overall percentage of CD45(hi) cells infiltrating the brain was not altered by IL-10 deficiency, paradoxically, despite elevated chemokine levels, reduced T lymphocyte (CD8+) and natural killer (NK) (CD49b+) cell infiltration into the brain was observed in IL-10-deficient animals. This decreased lymphocyte infiltration was associated with elevated levels of the lymph node homing receptor L-selectin/CD62L on CD8+ T cells. Lymph node cells obtained from MCMV-infected mice deficient in IL-10 also displayed reduced migration towards CXCL10 when compared to wild-type animals. Taken together, these data show that despite elevated chemokine levels, absence of IL-10 results in reduced lymphocyte infiltration into MCMV-infected brains.