This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)
All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission System of respective journal.
The canonical Wnt signaling pathway stabilizes
-catenin, which translocates into nucleus and complexes with the TCF1
transcription factor to modulate gene expression. This signaling cascade is known to critically regulate normal T cell
development; however, its physiological roles in mature CD8
T cell responses are less known. Using a Listeria monocytogenes
infection model, we found that ectopic expression of TCF1 and stabilized
-catenin limited effector CD8
T cell expansion but
augmented the pool of antigen-specific memory CD8
T cells. These memory CD8
T cells expanded to a larger number of
secondary effectors and cleared bacteria faster when the immunized mice were rechallenged with virulent L. monocytogenes. On
the other hand, TCF1 deficiency compromised production of memory CD8
T cells and impaired their differentiation towards a
central memory phenotype. Moreover, TCF1-deficient memory CD8
T cells were progressively lost over time, exhibiting reduced
expression of the anti-apoptotic molecule Bcl-2, interleukin-2 receptor
chain and diminished IL-15-driven proliferation.
Mechanistically, TCF1 was directly associated with the Eomes allele, and Eomes expression was modulated by the Wnt signaling
pathway in na?ve and memory CD8
T cells. Importantly, forced expression of Eomes partly protected TCF1-deficient memory
T cells from time-dependent attrition. Our studies thus indicate that the Wnt-TCF pathway is both necessary and sufficient
to promote differentiation and longevity of memory CD8
T cells. The Wnt-TCF1 pathway can thus be explored to improve
vaccine/adjuvant design, aiming for enhanced protective immunity
Xue completed his Ph.D with Dr. Arata Ichiyama in 2000 (Hamamatsu University College of Medicine, Japan) and postdoctoral fellowship with Dr.
Warren Leonard in 2006 (National Heart, Lung, and Blood Institute, NIH). He is currently an associate professor at Department of Microbiology, the
University of Iowa. His primary research interest focuses on transcriptional regulation of T cell development and mature T cell responses.
Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals