This article examined the role of T cells in acute renal failure (ARF). In vitro, ARF can be studied by performing bilateral ischemia (BI) on both kidneys in mice. This is done by clamping both the right and left kidney peduncles for around 22 minutes, restricting blood flow to both kidneys. After 22 minutes, the clamps are removed, and blood flow returns to the kidney.
Of course, ischemia-reperfusion injury results from doing BI on the kidneys. This causes pro inflammatory cytokines to be released throughout the blood, thus damaging other parts of the body. Recently, it was found that T cells are directly involved with ischemia reperfusion injury (Savransky et. Al, 2006).
Researchers in this article tested their hypothesis by looking at mice with deficient T cell receptors (TCR). They found that mice lacking the TCR were essentially protected against ischemia reperfusion injury; specifically, deficient TCR mice had a lower level of TNF-α and IL-6 (Savransky et. Al, 2006). The researchers used techniques like flow cytometry to confirm their TCR deficient mice were truly deficient, as well as an myeloperoxidase (MPO) assay to determine if neutrophils and macrophages had infiltrated the kidney tissue. However, they found no significant difference in neutrophil and macrophage infiltration at 24 hr between WT and TCR deficient mice (Savransky et. Al, 2006).
I personally found this article interesting because of the nature of my work. I do research on kidney failure and I thought it was great to find an article that correlates between my research and the topics of this class. I’m curious to know if anyone has further tested the data these researchers found by depleting macrophages in WT mice. Specifically, if you inject WT mice with LEC (liposome encapsulating clodronate, a macrophage ‘killer’) and then perform BI in the same fashion as these researchers, would you also get decreased TNF-α and IL-6 results?
Reference
“Role of the T-cell receptor in kidney ischemia-reperfusion injury.”
V Savransky, R R Molls, M Burne-Taney, C-C Chien, L Racusen and H Rabb.
Kidney International (2006) 69, 233-238.
3 comments:
Wow, do you think other examples of ischaemia-reperfusion injury (IRI) might also involve T cells? Stroke and heart attack models, for example?
Actually, I just went to PubMed and it appears that T cells are important in IRI generallly; and that drugs used to suppress T cells in, say, transplantation are useful in treating or preventing IRI. This seems to be a comprehensive review:
Ischemia-reperfusion and immediate T cell responses. Huang Y, Rabb H, Womer KL. Cell Immunol. 2007 (July); 248:4-11.
This was what I was wondering about as well - the implications of immulogical backfire with the reintroduction of perfusion to ischemic tissue following an MI or CVA. I found reference to this issue in an article which compared serum levels of both antibody and sICAM-1 and sVACM-1 (T cell response markers) in groups of 1) normal patients, 2) 1 week post-MI patients, and 3) 2 week and 2 month post-MI patients. Antibody levels, IgG and IgM, were higher than the normal group in group 2) and stayed elevated in group 3). T cell response marker levels were also elevated in group 2) and only sVCAM-1 was elevated in group 3). This brings up the clinical question of when to intervene and when not to, given the backlash of damage caused by "all of a sudden" reperfusion. Or could a slower rate of reperfusion eliminate some of this effect? Should we maybe rethink just reopening a block? For those that suffer silent MIs out of the hospital setting and their body responds, instead of by reperfusion, but by building alternative routes to oxygenate ischemic tissue, are they better off sometimes? This brings up a lot of clinical application!
Reference:
Interplay of antibody and T cell responses in acute myocardial infarction. Elahi, Vjayakumar, Lichstein, and Mokhtarian; Journal of Laboratory and Clinical Medicine, Volume 138, Issue 2, August 2001.
I am not familiar with work being done in IRI with macrophages in the renal model. But Joshua M. Thurman in the Renal department at UCSHC has published some great work looking at the role of the alternative pathway in IRI of the kidney as well as the role of an anti- Factor B antibody in preventing injury and ameliorating injury in traumatic brain injury (work now being done at Denver Health). There is a good review as well to look at
Thurman JM. Triggers of inflammation after renal ischemia/reperfusion. Clinical Immunology. 123(1):7-13, 2007 Apr
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