The fate of mature T lymphocytes might be a lot more flexible than previously thought. New research from the RIKEN Center for Allergy and Immunology (RCAI) in Japan and La Jolla Institute for Allergy and Immunology (LIAI) in the USA shows for the first time that mature CD4+ helper T lymphocytes can be re-programed to become killer-like CD8+ T lymphocytes and gain killing functions.
The findings are reported today in the journal Nature Immunology, by a team of researchers led by Ichiro Taniuchi from RIKEN and Hilde Cheroutre from La Jolla. The team show using transgenic mice that mature CD4+ helper T lymphocytes that have lost the transcription factor ThPOK express genes specific to CD8+ killer T lymphocytes upon exposure to a specific environmental stimulation such as the gut. This turns them into killer cells that might act to control infection.
CD4+ helper T lymphocytes and CD8+ killer T lymphocytes are important players in the body's defense mechanism against infection. CD4+ helper T lymphocytes normally only assist other cells of the immune system during an infection, whereas CD8+ killer T cells are the main actors in the elimination of infected cells.
Both types of cells are generated in the thymus, where their early precursors develop first into cells bearing both CD4 and CD8 markers. These CD4+ CD8+ cells then differentiate into cells bearing either the CD4 or CD8 marker and take on either a helper (CD4+) or killer (CD8+) fate.
The transcription factor ThPOK is known to play a crucial role in the fate determination of T lymphocytes in the thymus. It represses genes specific to CD8+ cells in precursors of helper T cells and prevents these cells from differentiating into CD8+ killer cells. The expression of ThPOK continues in mature CD4+ helper T cells and is repressed in mature CD8+ cells.
In the study, Taniuchi, Cheroutre and colleagues show that upon deactivation of ThPOK, mature CD4+ T cells revert back to bearing both CD4 and CD8 markers in the mouse intestine. By analyzing RNA extracted from ThPOK-negative CD4+ CD8+ cells, the researchers demonstrate that the cells express various CD8+ cell-specific genes encoding for cytolitic proteins and that they have effectively differentiated into CD8+ killer T cells.
The authors conclude: "The unexpected plasticity of mature CD4+ T cells to differentiate into CD8+ cytolitic cells expands the functional capabilities of CD4+ T cells. It is possible that CD4+ T cells are also involved in direct protective functions and provide the immune system with an alternative protective mechanism."
According to them, these cells may be recruited to help in the immune response at interfaces such as the skin or mucosae, where the rapid elimination of infected cells is crucial.
Taniuchi, I. Cheroutre, H. et al. "Transcriptional reprogramming of mature CD4+ helper T cells generates distinct MHC class II–restricted cytotoxic T lymphocytes." Nature Immunology, 2013, DOI: 10.1038/ni.2523
About RIKENRIKEN is Japan's flagship research institute devoted to basic and applied research. Over 2500 papers by RIKEN researchers are published every year in reputable scientific and technical journals, covering topics ranging across a broad spectrum of disciplines including physics, chemistry, biology, medical science and engineering. RIKEN's advanced research environment and strong emphasis on interdisciplinary collaboration has earned itself an unparalleled reputation for scientific excellence in Japan and around the world.
Juliette Savin | EurekAlert!
Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg
Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy