Vaccine and Infectious Disease Division

Mechanisms of mature T cell survival and differentiation

T cells possess the remarkable ability to differentiate into a large pool of short-lived effector cells and a small subset of long-lived memory cells after becoming activated following exposure to an antigen.  The memory cells share key characteristics with stem cells: they have an ability to self-renew by slow turnover and are long-lived.  Additionally, they share certain transcriptional characteristics with hematopoietic stem cells (HSC), but it remains to be determined how these T cells gain their memory phenotype. Understanding how memory T cells are generated and maintained would greatly advance development of vaccines and other therapies that rely on the immune system.

VIDD assistant member Dr. Martin Prlic, during his postdoctoral fellowship at the University of Washington, addressed this question by asking whether protein pathways known to be necessary for HSC self-renewal were also involved in the generation and maintenance of memory T cells.  Prlic generated mice whose mature T cells lack the protein β-catenin, an essential component of the regulatory pathway that controls HSC self-renewal and differentiation.  Through a series of tests in which the mice were challenged with a variety of pathogens, he determined that β-catenin expression was not required for the generation of functional memory T cells, and that T cells from the knock-out mice were indistinguishable from those of normal mice.  While the question of how memory T cell generation is regulated remains to be determined, this study provides the first evidence that there are multiple pathways by which different hematopoietic cells can self-renew and survive for long periods of time.

Prlic M, Bevan MJ. Cutting Edge: β-Catenin Is Dispensable for T Cell Effector Differentiation, Memory Formation, and Recall Responses.  J Immunol. 2011 Aug 15;187(4):1542-6.