Following an immune cell's career path
Figure 1: The various classes of T cells are capable of responding to pathogenic threats and restraining the resulting immune response to avoid inflicting damage on host tissues. Credit: Dr Triche, National Cancer Institute, USA
The immune system produces diverse varieties of T cells (Fig. 1), such as pathogen-destroying cytotoxic T cells and immune response-boosting helper T cells. Regulatory T (Treg) cells restrain these other cells and prevent the body from overreacting to threats or generating a dangerous autoimmune response.
Treg cells are usually identified by expression of the transcriptional regulator protein Foxp3, but new work from a team led by Shohei Hori of the RIKEN Research Center for Allergy and Immunology in Yokohama has demonstrated that this is not a reliable signature.
Several groups have obtained data suggesting that Treg cells can essentially change careers, losing their Foxp3 expression and transforming into other T cell types. However, findings from Hori and colleagues led them to propose an alternative heterogeneity model. Our observations suggested that these phenomena can be fully explained by a minor uncommitted population of Foxp3+ T cells without assuming reprogramming, he says. His group has now provided compelling evidence for this hypothesis by using a labeling technique that allowed them to distinguish cells currently expressing Foxp3 from those that are not, but which have expressed this protein in the past.
The researchers identified two groups of Foxp3-expressing cells that responded differently to an immune stimulus. Most expressed this protein stably and at high levels, and exhibited the functional characteristics of Treg cells. A minority fraction displayed transient bursts of Foxp3 expression, but ultimately developed into other T cell types. These exFoxp3 cells did not appear to represent reprogrammed Treg cells, but rather a separate pool of T cells that only produce this protein sporadically.
Interestingly, his team also learned that some Treg cells do enter a state where they stop expressing Foxp3, although they retain memory of their identity as Treg cells. This is achieved via chemical modifications to the DNA within the gene encoding Foxp3, and immune stimulation promptly leads to robust re-expression of this protein. This should force people to reconsider the popular but oversimplified view of Foxp3 as the master regulator of Treg cells, says Hori.
The events that determine this expression profile are therefore likely to prove more important in establishing cellular identity than the presence or absence of Foxp3. It has been speculated that the Treg lineage is determined by a higher-order regulatory pathway upstream of Foxp3, but the nature of this system is unknown, says Hori. In future work, he plans to partner with colleagues at other RIKEN laboratories to investigate this question more closely.
More information: Miyao, T., et al. Plasticity of Foxp3+ T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells. Immunity 36, 262275 (2012).
Komatsu, N., et al. Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. Proceedings of the National Academy of Sciences 106, 19031908 (2009).
Provided by RIKEN
- New insight into immune tolerance furthers understanding of autoimmune disease Sep 15, 2011 | not rated yet | 0
- Asthma and other allergies tied to absence of specialized cells Jul 17, 2008 | not rated yet | 0
- Researchers discover new molecular path to fight autoimmune diseases Mar 06, 2007 | not rated yet | 0
- Rheumatoid arthritis breakthrough Nov 12, 2008 | not rated yet | 0
- Ensuring the persistence of immune memory Sep 16, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
gravity is std. therefore can we rate a 'mass at height' by watts?
5 hours ago For example.... wind turbines are primarily listed by their wattage (1.5MW etc.) Presumably their output is varied according to rotational speed, so...
Calculating on-axis elements of a solenoid
17 hours ago I wanted to mention that this solenoid has many winds over many layers. The thickness of the windings is 2.4 inches coming off of the engineering...
latitude & longitude & air pressure
18 hours ago Hi there, I have a peculiar question. Imagine that you are in a earth position, obtained by google, that gives you the latitude and longitude....
Differences of Classical Mechanics when learned with Calc vs algebra?
21 hours ago what are the differences? Every example I find usually has a derivative or integral or some kind of calculus defined concept that seems to make it...
what is the distance traveled
May 22, 2013 A rough sketch of experiment. Image: http://i43.tinypic.com/14t4sk5.png the red dots represent a side view of path traveled, F is downward force...
Image of a Convex Lens Cut in Half Horizontally
May 22, 2013 Hello everyone, A friend of mine came up with this question in class and I really do not have a good answer. Suppose you have a convex lens...
- More from Physics Forums - Classical Physics
More news stories
(Medical Xpress)—Scientists at Emory Vaccine Center have shown that an immune regulatory molecule called IL-21 is needed for long-lasting antibody responses in mice against viral infections.
Immunology 6 hours ago | 5 / 5 (1) | 0 |
Human breastmilk responds quickly to protect the child when there is an infection in mothers or babies, according to new international research led by The University of Western Australia.
Immunology 7 hours ago | 5 / 5 (1) | 0
(Medical Xpress)—A research team, led by Jeremy Barr, a biology post-doctoral fellow, unveils a new immune system that protects humans and animals from infection.
Immunology May 20, 2013 | 4.8 / 5 (25) | 8 |
(Medical Xpress)—Scientists at King's College London have discovered that Vitamin D has the potential to significantly reduce the symptoms of asthma. The study, led by Professor Catherine Hawrylowicz from ...
Immunology May 20, 2013 | 5 / 5 (1) | 0 |
Little is known about why asthma develops, how it constricts the airway or why response to treatments varies between patients. Now, a team of researchers at Weill Cornell Medical College, Columbia University Medical Center ...
1 hour ago | not rated yet | 0 |
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as the sensation of ...
39 minutes ago | 5 / 5 (1) | 0 |
Teams of highly respected Alzheimer's researchers failed to replicate what appeared to be breakthrough results for the treatment of this brain disease when they were published last year in the journal Science.
39 minutes ago | not rated yet | 0 |
(Medical Xpress)—The human brain is able to identify individuals' voices by comparing them against an internal 'average voice' prototype, according to neuroscientists.
55 minutes ago | not rated yet | 0 |
An anti-cancer drug reverses memory deficits in an Alzheimer's disease mouse model, University of Pittsburgh Graduate School of Public Health researchers confirm in the journal Science.
33 minutes ago | not rated yet | 0 |
Since the discovery of Prontosil in 1932, sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections, from acne to chlamydia and pneumonia. However, their side effects can include serious neurological ...
39 minutes ago | not rated yet | 0 |