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.
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. Epub 2011 Jul 25. PubMed PMID: 21788440; PubMed Central PMCID: PMC3159846.
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. Epub 2010 Dec 17. PubMed PMID:21169546; PubMed Central PMCID: PMC3075597.
Gurung, P., Kucaba, T.A., Schoenberger, S.P., Ferguson, T.A., and Griffith, T.S. TRAIL-expressing CD8+ T cells mediate tolerance following soluble peptide-induced peripheral T cell deletion. Journal of Leukocyte Biology, Vol 88. [Epub ahead of print], PMID: 20807702, 2010.
Gurung, P., Kucaba, T., Ferguson, T.A., and Griffith, T.S. Activation-induced CD154 expression abrogates tolerance induced by apoptotic cells. The Journal of Immunology, Vol 183(10): 6114-6123. PMID 19841180, 2009.
Gurung, P., Young, B.M., Coleman, R.A., Wiechert, S., Turner, L.E., Ray, N.B., Waldschmidt, T.J., Legge, K.L., and Cook, R.T. Chronic ethanol induces inhibition of antigen-specific CD8+ but not CD4+ immunodominant T cell responses following Listeria monocytogenes inoculation. Journal of Lecukocyte Biology, Vol. 85(1): 34-83., PMID 18820175, PMCID: PMC2626766, 2009.
Young B.M., Wiechert, S., Coleman, R.A., Gurung, P., and Cook, R.T. Polyclonal and antigen-specific responses of T cells and T cell subsets. Methods Mol Biol., Vol. 447: 277-94., PMID 18369925, 2008.