My thesis project looks at the role of dead cells in regulating immune responses within our body. Cell death can occur primarily by two main processes, apoptosis and necrosis. Apoptosis is also known as programmed cell death and does not induce any immune response, whereas necrosis is an accidental cell death due to trauma or injury and is highly inflammatory.
Naïve apoptotic cells do not mature dendritic cells, whereas pre-activated apoptotic cells do. Thus my first project is to elucidate the mechanisms that result in these two different outcomes.
Peripheral tolerance is a mechanism by which self-reactive T cells that escape thymic deletion are kept in check. Several studies have shown that peptide-induce deletion of Tg-CD4+ T cells induce tolerance in the mice to that same antigen/peptide. My second project is to understand the mechanisms that are involved in this induction of tolerance.
Brincks EL, Gurung P, Langlois RA, Hemann EA, Legge KL, Griffith TS. The
magnitude of the T cell response to a clinically significant dose of influenza
virus is regulated by TRAIL. J Immunol. 2011 Nov 1;187(9):4581-8. doi:
10.4049/jimmunol.1002241. Epub 2011 Sep 21. PubMed PMID: 21940678; PubMed Central PMCID: PMC3197947.
Gurung P, Rai D, Condotta SA, Babcock JC, Badovinac VP, Griffith TS. Immune unresponsiveness to secondary heterologous bacterial infection after sepsis induction is TRAIL dependent. J Immunol. 2011 Sep 1;187(5):2148-54. doi:10.4049/jimmunol.1101180. Epub 2011 Jul 25. PubMed PMID: 21788440; PubMed Central
Griffith TS, Brincks EL, Gurung P, Kucaba TA, Ferguson TA. Systemic
immunological tolerance to ocular antigens is mediated by TRAIL-expressing CD8+ T cells. J Immunol. 2011 Jan 15;186(2):791-8. doi: 10.4049/jimmunol.1002678. Epub 2010 Dec 17. PubMed PMID: 21169546; PubMed Central PMCID: PMC3075597.
Gurung P, Kucaba TA, Schoenberger SP, Ferguson TA, Griffith TS.
TRAIL-expressing CD8+ T cells mediate tolerance following soluble peptide-induced peripheral T cell deletion. J Leukoc Biol. 2010 Dec;88(6):1217-25. doi:10.1189/jlb.0610343. Epub 2010 Aug 31. PubMed PMID: 20807702; PubMed Central PMCID: PMC2996898.
Gurung P, Kucaba TA, Ferguson TA, Griffith TS. Activation-induced CD154
expression abrogates tolerance induced by apoptotic cells. J Immunol. 2009 Nov 15;183(10):6114-23. doi: 10.4049/jimmunol.0901676. Epub 2009 Oct 19. PubMed PMID:19841180; PubMed Central PMCID: PMC2783861.