Research in the Gumperz Lab


 

We are interested in how innate T lymphocytes contribute to immune responses, and how these cells may be used therapeutically to treat or prevent disease.

 

We focus mainly on T cells that recognize lipid antigens presented by CD1 molecules.  Natural Killer T (NKT) cells are one such subset.  They recognize specific self lipids as antigens presented by CD1d molecules and influence the functions of many other types of immune cells.

We have found that one of the self lipids recognized by NKT cells is a molecule called lysophosphatidylcholine (LPC).  LPC is produced during the initiation of biosynthesis of inflammatory lipid mediators, and thus it may signal to NKT cells that an inflammatory response is underway. 

Crystal structure of the TCR of aniNKT cell recognizing LPC bound to CD1d.  From Lopez-Sagaseta et al., EMBO J. 2012 Mar 6;31(8):2047-59

Human NKT cells producing IFN-g (green) in response to Dendritic Cells.  From Wang et al., JExp Med. 2012 May 7;209(5):987-1000

We have also recently demonstrated that self antigen recognition causes epigenetic changes in the acetylation of histones of human NKT cells that enables them for a limited time to produce IFN-g independently of antigen recognition in response to cytokines made by antigen presenting cells.

We are interested in understanding how NKT cells contribute to inflammatory responses

From Fox et al., Microbes Infect. 2010 Dec;12(14-15):1125-33

Human T cells labeled in green form long-lasting clusters with human monocyte-derived DCs (red), but not with NKT-instructed DCs.  From Hegde et al., J Autoimmun. 2011 Aug;37(1):28-38

We are also interested in understanding how NKT cells regulate immune responses by directing the differentiation of tolerogenic DCs:  We have previously observed that human monocytes that are exposed to NKT cells differentiate into DCs that are refractory to contact with T cells and that do not polarize T cells towards a TH1 phenotype.

We are now testing the tolerogenic impact of NKT-instructed DCs on the development of GVHD and investigating their ability to transfer HIIV to T cells.

To model the functions of human innate lymphocytes in vivo, we are using SCID mice engrafted with human hematopoietic stem cells and thymic tissue.

                                    From Lockridge et al., PLoS One. 2011;6(6):e21701