Abstract
Purpose: :
ECOR is an animal model of a progressive retinal degeneration induced by murine hepatitis virus (MHV). An acute retinal inflammation results in a chronic, immune-associated retinal degeneration and autoimmune reactivity in susceptible BALB/c mice, while acute retinal inflammation is followed by a complete recovery in resistant CD-1 mice. Recently we found that the innate immune response is significantly more intense in BABL/c mice. In this study we compared adaptive cellular immune responses to the virus locally and systemically in BALB/c and CD-1 mice.
Methods: :
BALB/c and CD-1 mice were inoculated with MHV (JHM strain) or with PBS by the intravitreal route. Tissue samples (retina, spleen, and lymph nodes) were collected from three groups of mice, virus infected, mock infected and untreated, at 2, 4, 7, 10, 14 and 21 days post infection (p.i.), for cytokine and chemokine detection by EIA and CBA and for FACS analysis.
Results: :
Histopathologic analysis revealed intense retinal inflammation at day 7 p.i. Inflammation appeared to be more intense in CD-1 mice. FACS analysis showed higher frequency of CD8 T cells infiltrating into the eyes of CD-1 on day 7 compared to BALB/c (24.3% versus 13.7%). Moreover, local retinal cytokine and chemokine production was more intense in CD-1 than BALB/c. Compared to BALB/c, higher levels of IL-1beta, IL-6, TNF-alpha, IFN-gamma and IL-10 were detected in CD-1 at days 7 and 10 p.i. and this was associated with increased levels of chemokine CXCL9, CXCL10, CCL3, CCL4 and CCL5. Similar to the retina, an increased cytokine and chemokine profile was observed at in the CD-1 draining lymph nodes. Compared to BALB/c, higher levels of IFN-gamma, IL-1beta, IL-6, and IL-12p70 were detected in CD-1 at days 7, 10, or 14, respectively.
Conclusions: :
Our data demonstrate that retinal degeneration seen in susceptible BALB/c mice is associated with less intense local and systemic adaptive immune responses in the acute phase of the infection.
Keywords: cytokines/chemokines • retinal degenerations: cell biology • inflammation