In previous work, Dr. Daniel Lacorazza, assistant professor of pathology at BCM, along with his research team, identified a transcription factor, ELF4, which regulates blood stem cells. A transcription factor is a protein that regulates how genes are translated into a form that leads to the making of the proteins associated with them.
"We knew ELF4 played a role in maintaining T cells," said Lacorazza, who is the principal investigator of the current study. "What we discovered was that ELF4 activates an inhibitor that leads to cell arrest, stopping naive T cells from proliferation."
A population of naïve CD8 T-cell is always circulating in the body and maintained at a constant level. Memory T cells are created when naïve CD8 T cells are activated to fight intracellular pathogens such as viruses or bacteria. The fight against infections prompts creation of memory T cells that then "remember" antigens or proteins found on cells infected with viruses or bacteria. In the future when same infections arise, memory T-cell enhances the body's ability to fight them.
Lacorazza and his research team focused on how ELF4 affected the process of inhibiting proliferation of CD8 T cells. Using mice generated to lack ELF4, researchers found that CD8 T-cells grew over time and acquired a "memory phenotype" without being exposed to any type of infections. At the same time, they determined that expression of the tumor suppressor gene called KLF4 was reduced in these mice.
"We discovered that ELF4 directly activates the tumor suppressor KLF4, which signals cell cycle arrest in naïve CD8 T cells," Lacorazza said. "This inhibitory process is important to T cells because it stops them from proliferating out of control." Cell cycle arrest means the cells do not go through the normal events of their life cycles: growth, replication and division. The description of cell intrinsic regulation of quiescence in normal T cells will provide insights on the pathobiology of lymphoid malignancies.
The researchers then immunized mice deficient for ELF4 to test their immune response. These mice had a larger memory T cell response, indicating that the absence of ELF4 eliminated control over the proliferation of CD8 T cells.
"If we can control ELF4 activation during vaccination, we can enhance long-term immune response, making a vaccine more effective," Lacorazza said.
"We could enhance in vitro T cell activation of T cells extracted from patients to heighten immune response", said Lacorazza. "In addition, a future line of study is to determine whether deletion of KLF4 expands pre-leukemic clones leading to overt leukemia in pediatric patients".
Lacorazza said these are still hypotheses, but understanding the process that controls T cell proliferation will help in future research.
Other researchers who were a part of the study include Takeshi Yamada and Chun Shik Park, both postdoctoral associates in the Pathology Department at BCM, and Maksim Mamonkin, graduate student in the Department of Immunology at BCM.
Funding for the research was provided by the National Institutes of Health, the Curtis Hankamer Basic Research Fund (Junion-Faculty Seed Award) and a pilot project of the Dan Duncan Cancer Center at BCM.
For more information on basic science research at Baylor College of Medicine, please go to www.bcm.edu/news or www.bcm.edu/fromthelab.
Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)
CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
19.01.2017 | Earth Sciences
19.01.2017 | Life Sciences
19.01.2017 | Physics and Astronomy