Regulation of CD1d-Medicated Antigen Presentation by Nf1
Abstract
The goal of this Exploration-Hypothesis Development Award is to analyze the role of NF1 in the functional expression of CD1d. During the second year of the award, we have analyzed the ability of bone marrow-derived dendritic cells (BMDC) from wildtype (WT) and NF1+/- mice to stimulate fresh NKT cells. The original hypothesis was that we would observe more Th2 (i.e., anti-inflammatory)--as opposed to Th1 (i.e., pro-inflammatory)--cytokine production by NKT cells. Our results suggest that NKT cells from both WT and NF1+/- mice can produce both Th1 and Th2 cytokines at comparable levels. As indicated last year, when analyzing the level of cell surface CD1d, it was observed that BMDC generated from NF1+/- mice expressed ~75% of the WT level of CD1d, but were able to stimulate NKT cells as well as those from WT mice. However, we have found a reduction in a B220+CD1d-hi population in splenocytes from NF1 +/- mice. This suggests that NF1 plays an important role in the qualitative expression of CD1d. Furthermore, NKT cells from NF1+/- mice are more activated at baseline, than those from WT mice. In line with this observation, RMA/S tumor growth in NF1+/-mice was reduced compared to WT mice. Therefore, these data strongly suggest that NF1 plays an important (albeit inhibitory) role in the host s innate antitumor immune response (i.e., CD1d/NKT cell axis)
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2012
- Accession Number
- ADA560605
Entities
People
- Randy Brutkiewicz
Organizations
- Indiana University