4-1BBL deficiency abrogates splenic hypotrophy observed following LCMV clone 13 infection in mice (P6130)

• Published in: The Journal of immunology (1950) 2013-05, Vol.190 (1_Supplement), p.128-128.16
• Main Authors: Mbanwi, Achire, Wang, Chao, Watts, Tania
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.190.Supp.128.16

Mice infected with lymphocytic choriomeningitis virus (LCMV) clone 13 develop a prolonged viral infection that is used as a model to study HIV infection in humans. The tumor necrosis factor (TNF) receptor family member 4-1BB, and its ligand, 4-1BBL, have been established as powerful modulators of anti-viral immunity. Here we reveal a novel role for 4-1BBL in splenic contraction following LCMV infection. At day 8 post-infection, WT and 4-1BBL-/- mice show spleens that are 2 times the average pre-infection weight. However, by 2 months following infection, a time point at which virus is no longer detectable in the spleen, WT spleens show splenic atrophy, contracting up to 50% below baseline, whereas 4-1BBL-/- spleens contract back to baseline size. Interestingly, although 4-1BBL-/- spleens show increased cellularity, there is a deficit in the frequency of a B220-TCRβ-CD11bintCD11cintNK1.1+ natural killer (NK) cell population. The change in spleen size and NK population is observed in 4-1BBL-/-, but not 4-1BB-/- mice, suggesting a 4-1BB-independent 4-1BBL mechanism. Using bone marrow chimeras, as well as NK depleting antibodies, work is in progress to elucidate the cell type on which 4-1BBL is required for these effects and the potential role for NK cells in controlling splenic contraction following viral infection. This study suggests a novel role for 4-1BBL in splenic contraction and could have important implications for understanding the resolution of inflammatory conditions.