Tuesday, May 18, 2010

New evidence that incompetent T regs are a root cause of asthma perhaps allergy and autoimmune as well

We know from previous research that the T reg or"good guy" cells in folks with autoimmune disease seemed to be 'incompetent'. They appeared to not be able to turn off the inappropriate autoimmune reaction started by the auto reactive antibodies ( think tiny chemical guided missiles) produced by 'rogue" B cells and continued and increased by the 'bad guy' T effector cells. The autoantibodies label our cells as needing to be attacked and the T effectors enthusiastically follow their directions.

We think we know that T regs in folks with normally functioning immune systems seem able to tamp down the autoimmune reactions before they start.

Apparently those of us suffering from one of the 80 or so named autoimmune disease could use properly functioning T regs. Perhaps the T regs working as they should would be enough to stop disease progression. No one is quite sure, but it is beginning to appear more and more like that may be true.

Now we have evidence that malfunctioning T regs may be at the heart of asthma as well. It seems that folks with asthma have lots of extra T regs in their lungs. Far more than in the lungs of folks without asthma. This is what we would expect if the job of T regs was to settle down over active immune responses like inflammation in the lungs.

You see the T regs of those of us with asthma still answer the call to stop the autoimmune inflammatory damage but when they get to the correct site in the body, they are incompetent. They cannot do their job. Hence more and more T regs are called in by the out of control inflammatory signals being given off by the damaged tissue. Sadly no matter how many T regs arrive, they cannot do anything to help.

If a way could be found to fix our T regs with some form of the multiple ways we know to change gene expression than we might get competent correctly functioning T regs. Please God from my hand to your ear. Then at least some if not all asthma, allergy, eczema, and autoimmune disease might be able to be stopped.

That day is still a long way off. But heroic lab scientist keep chipping away at what we do not know so that one day we will know enough so no one has to suffer from these horrors again.

Below is an abstract of a study done by fine folks at the University of Manchester which found the extra T regs in the lungs of asthma patients thus linking a possible cause of asthma with a probable cause of other autoimmune disease. Note when they mention 'effector lymphocyte activity' they are talking about our old nemesis, the 'bad guy' cells, T effectors. T effs attack our tissues in autoimmune disease.

One might infer that some kind of plasmapheresis or shifting/sorting of our blood cells to eliminate T effectors would stop disease, but sadly the T effs may be just a different side of the same coin that is T regs. Eliminate T effectors and then our incompetent T regs would convert into competent T effectors. Some studies appear to show that T effs change into T regs and vice versa.

The likely problem that we, the afflicted, have with our immune system, then, is that our T regs somehow do not function correctly to stop inflammation in the T reg configuration, but when they are in the T effector configuration they can function to cause inflammation, tissue damage and the killing of pathogens.

Probably if the T effectors configuration did not function correctly we would have died of infection long ago. So instead of hating them for the pain they cause, we should be glad that they can function to stop disease. They just are like unruly guard dogs that attack everything friend and foe alike. Hopefully someday we will have a method to train them to behave.

Here is the abstract:

Chest. 2010 May 7. [Epub ahead of print]
Increased airway T regulatory cells in asthmatic subjects.
Smyth LJ, Eustace A, Kolsum U, Blaikely J, Singh D.
University of Manchester, NIHR Translational Research Facility, Manchester Academic Health Science Centre, University Hospital Of South Manchester Foundation Trust, Southmoor Road, Manchester, UK. M23 9LT.

BACKGROUND: Tregulatory cells (Tregs) may play a role in suppression of effector lymphocyte activity in asthma. We hypothesized that Treg numbers would be increased in patients with more severe asthma. We also investigated the regulatory function of CD4 cells by expression of CTLA4, and the number of these cells that are intra-epithelial lymphocytes expressing CD103.

OBJECTIVES: The primary aim was to investigate Treg numbers in the BAL of patients with moderate to severe asthma compared to mild asthma and healthy controls. The secondary aim was to investigate BAL CD4+CTLA4 and CD4+CD103 expression in these groups.

METHODS: Airway lymphocytes obtained by bronchoscopy from healthy controls (6), patients with mild (15) and moderate to severe asthma (13) were characterised by multi-parameter flow cytometric analysis using 3 methods to determine the numbers of CD4+ Treg cells: CD4+CD25(bright), CD4+CD25+CD127-, CD4+FoxP3+.

RESULTS: %CD4+FoxP3+ Tregs were increased in BAL of patients with moderate to severe asthma (median 4.8%) compared to both mild asthma patients (median 2.5%, p=0.03) and healthy subjects (median 0.95, p=0.003). Similar findings were observed for CD4+CD25+CD127- Treg numbers, but not CD4CD25(bright). CD4+ CTLA4 and CD103 expression were raised in moderate to severe asthma patients compared to mild asthma and healthy controls.

CONCLUSIONS: The number of cells displaying regulatory capacity, either through FoxP3 expression or CTLA4 expression, are increased in moderate to severe asthma. CD4+CD103+ intra-epithelial lymphocytes can be retained at tissue sites of inflammation; our findings indicate a role for these cells in asthma pathophysiology.

PMID: 20453071 [PubMed - as supplied by publisher]

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