The adaptive immune system depends on the vast proliferation of anti-pathogen lymphocytes. In order to proliferate in this way, lymphocytes have to maintain their replicative capacity in the face of anti-proliferative signals delivered by inflammation. My prior work has studied how the signal for terminal differentiation in these cells could be linked to the magnitude of their proliferation. (see figure)
My current focus is the study of how responding adaptive immune lymphocytes avoid the anti-proliferative signals of inflammation. This work has received substantial support from the MRC and hopes to identify new pathways for the therapeutic manipulation of immune responses. These scientific objectives stem directly from my clinical work, based at Addenbrooke’s hospital, where I look after patients with primary and secondary immunodeficiency. An ongoing research priority within our clinical department is the identification of novel immunodeficiencies and therapies.
Blimp-1 ; T cells ; CD8+ ; differentiation ; interleukin ; memory cells
Dickinson RE, Milne P, Jardine L, Zandi S, Swierczek SI, McGovern N, Cookson S, Ferozepurwalla Z, Langridge A, Pagan S, Gennery A, Heiskanen-Kosma T,Hämäläinen S, Seppänen M, Helbert M, Tholouli E, Gambineri E, Reykdal S, Gottfreðsson M, Thaventhiran JE, Morris E, Hirschfield G, Richter AG, Jolles S,Bacon CM, Hambleton S, Haniffa M, Bryceson Y, Allen C, Prchal JT, Dick JE, Bigley V, Collin M. The evolution of cellular deficiency in GATA2 mutation. Blood. 2013 Dec 17. [Epub ahead of print]
Thaventhiran JE, Fearon DT, Gattinoni L. Transcriptional regulation of effector and memory CD8(+) T cell fates. Curr Opin Immunol. 2013 Jun;25(3):321-8.
James E. Thaventhiran and Douglas T. Fearon Control of HIV infection: Escape from the shadow of Blimp-1 European Journal of Immunology 2013 Volume 43, Issue 2, February 2013, Pages: 323–326
Thaventhiran JE, Hoffmann A, Magiera L, de la Roche M, Lingel H, Brunner-Weinzierl M, Fearon DT. Activation of the Hippo pathway by CTLA-4 regulates the expression of Blimp-1 in the CD8+ T cell. Proc Natl Acad Sci U S A. 2012 Aug 14;109(33)
Carr JM, Carrasco MJ, Thaventhiran JE, Bambrough PJ, Kraman M, Edwards AD, Al-Shamkhani A, Fearon DT. CD27 mediates interleukin-2-independent clonal expansion of the CD8+ T cell without effector differentiation. Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19454-9
Fearon DT, Carr JM, Telaranta A, Carrasco MJ, Thaventhiran JE. The rationale for the IL-2-independent generation of the self-renewing central memory CD8+ T cells. Immunol Rev. 2006 Jun;211:104-18.