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A Mouse Model of Clonal CD8+ T Lymphocyte-Mediated Alopecia Areata Progressing to Alopecia Universalis
Rajshekhar Alli*, Phuong Nguyen*, Kelli Boyd*,†, John P. Sundberg‡ and Terrence L. Geiger*
+ Author Affiliations
*Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105;
†Department of Pathology, Vanderbilt University, Nashville, TN 37232; and
‡The Jackson Laboratory, Bar Harbor, ME 04609
Address correspondence and reprint requests to Dr. Terrence L. Geiger, Department of Pathology, St. Jude Children’s Research Hospital, 262 St. Jude Place, D-4047, Memphis, TN 38105. E-mail address: terrence.geiger@stjude.org
Abstract
Alopecia areata is among the most prevalent autoimmune diseases, yet compared with other autoimmune conditions, it is not well studied. This in part results from limitations in the C3H/HeJ mouse and DEBR rat model systems most commonly used to study the disease, which display a low frequency and late onset. We describe a novel high-incidence model for spontaneous alopecia areata. The 1MOG244 T cell expresses dual TCRA chains, one of which, when combined with the single TCRB present, promotes the development of CD8+ T cells with specificity for hair follicles. Retroviral transgenic mice expressing this TCR develop spontaneous alopecia areata at nearly 100% incidence. Disease initially follows a reticular pattern, with regionally cyclic episodes of hair loss and regrowth, and ultimately progresses to alopecia universalis. Alopecia development is associated with CD8+ T cell activation, migration into the intrafollicular region, and hair follicle destruction. The disease may be adoptively transferred with T lymphocytes and is class I and not class II MHC-dependent. Pathologic T cells primarily express IFNG and IL-17 early in disease, with dramatic increases in cytokine production and recruitment of IL-4 and IL-10 production with disease progression. Inhibition of individual cytokines did not significantly alter disease incidence, potentially indicating redundancy in cytokine responses. These results therefore characterize a new high-incidence model for alopecia areata in C57BL/6J mice, the first to our knowledge to apply a monoclonal TCR, and indicate that class I MHC-restricted CD8+ T lymphocytes can independently mediate the pathologic response.
Footnotes
This work was supported by National Institutes of Health Grants R01 AI056153 (to T.L.G.) and R01 AR056635 (to J.P.S.), the American Lebanese Syrian Associated Charities/St. Jude Children’s Research Hospital (to R.A., P.N., K.B., and T.L.G.), and the North American Hair Research Society (to K.B.).
The online version of this article contains supplemental material.
Received March 8, 2011.
Accepted October 22, 2011.
Copyright © 2011 by The American Association of Immunologists This is the all text and i copy and past it all as it was now i don't really get the text because all the scientific words, what does retroviral transgenic mice even mean?? Does it mean a mice that had retrovirus and that passed it to the other mice?Sadly i think they mean that, am not sure did look up some retroviruses if this is the case they are contagious and remain in body for life cause all kind of problems and even breast cancer that i didn't even know was a cause from virus and leukemia to now seems for alopecia as well..
Thank you Karen and Lily i hope am wrong but thing about retroviruses are contagious try body fluids or blood only, so if someone have it this is the only way you can get it please do ask him Karen and let us know i my self don't get what they mean i will look fore more and more info about this to see if maybe i got it wrong so far can;t find nothing they say everywhere with same thing as in this text
disaster. I read whole article... please calm down.. as much I believe that development of AA and AU is environmentally dependant (based on the observation of my friend, boyfriend and three other guys affected with AU in the last 2 years in my university) and possibily caused by virus/mould/chemical compound... this article certainly does not suggest it is caused by retrovirus!! they used a retrovirus to inject modified T cells receptors into healthy mice... and observe how the disease is developing in 'infected mice'... there is nothing new in this apart from a proof that it is the T cells mutation that leads to alopecia and it has potential of spreading, therefore causing AA to develop into AU..... nothing new apart from a new model of patomechanism.. they dont explain though how spontanious T cell receptor (TCR) mutation occurs in people with alopecia....
this is more optimistic. http://www.hairloss-research.com/
Thank you Dom for posting the thing this blog is poking me in the eye is because i found the all research http://www.nature.com/jid/journal/v111/n5/full/5600181a.html#bib21 this is the link thing is cells infect the mice try skin surgery i also found the same thing to Cutaneous Lymphoma and Alzeheimer's disease both are spread try same way as julija posted this they injected it in healthy mice and they got sick but for this 2 diseases the cause is found HTLV a retrovirus from tupe 1 to tupe 9 not sure how much retroviruses are there but this ones was the causes now the research is well to not say same but it is same at the research to alopecia with the mouses and same procedure same reaction am fearing it is a retrovirus no matter how much ppl say it aint in very healthy persons the retrovirus will be killed but if your not so healthy your doomed lets face it today with so much poison in the air,food,water no one is 100% healthy well very rare once you get the retrovirus and if manages to get in your cells it will take up to 8-10 years you to develop signs and have it for life pass it on to child..Sorry for eror spells am way to tired to type was lot on computer shall post a blog for this before going to bed i really hope is not contagious this what we have i have a gf she is only 19 and i fear if i could pass this to her i really strongly thing is a retrovirus why they didn't find it by now is because there was very litle research for alopecia but am sure they will find the correct type and than shall have corect cure
Thank you Dom hope you are right as more am reading for research more and more they freak me out idk if you read the link i add in my other post, but i really don't get why healthy mice got alopecia from a crafted skin part on there body from affected mice try surgery i don't think genes can be pass try surgery on other mice...am so messed up now and fear to the bone for my gf because retroviruses or prions are only contagious try body fluid or blood and because they said try surgery healthy mice got the same problem makes me wonder.
HI julija and all that will read this here is 1 more evidence and yes julija seems you really did got it from your ex he had AU right i read it in your other blog same happened to me with my ex gf she had AU to and years later i slowly started developing it i thinked was just coincidence but yea right......For all those that are not yet convinced: Alopecia à Deux: Simultaneous Occurrence of Alopecia in a Husband and Wife
Alicia D. Zalka, MD; Jean A. Byarlay, MD; Lowell A. Goldsmith, MD
Department of Dermatology University of Rochester School of Medicine and Dentistry 601 Elmwood Ave Box 697 Rochester, NY 14642
Arch Dermatol. 1994;130(3):390-392.
Since this article does not have an abstract, we have provided the first 150 words of the full text PDF and any section headings.
The incidence of alopecia areata (AA) in the general population is 17.2 per 100 000 per year.1 Within dermatology practices, it affects one to four per 100 patients.2 For an individual, the lifetime risk of AA is about 1%.3 There are reports of AA among siblings,4 including reports of identical twins affected simultaneously.5 Psychosocial causal factors such as stress are implicated in the onset of AA.6-8 Men appear to be equally at risk for developing AA as are women.
Folie à deux is an uncommon entity, referring to the transference of delusional ideas and/or bizarre behaviors from one person to another who are in a close relationship. The result of folie à deux is the sharing of a unique characteristic, which is simultaneously expressed among two or more individuals. We present two cases of AA occurring at the same time in a married couple. . . . [Full Text PDF of this Article....Check this out as well is for sure a retrovirus or prion retroviruses can remain silent in the body for up to 20,30 years and that explains a lot HTLV is one of them is spread from infected person to the partner and than to the child in some very healthy persons it wont show up until there really old age depending when they got infected prions work sort of the same way and both retroviruses and prions can be pass from generation to generation because it never got cured in the first place so there is the "auto imune desease" I know 2 ppl that got alopecia from there exes i am one of thous and this article here just prove it even more what is weird i dig up this things from even 1945 and 1988 and what pisses me off is they did't even said public that has a risk to be spread no matter what it is they proved it with the mouses, couples and so on and yet didn't made it world wide known yes genetic can play a role and chemical but is not the main cause and they should have made public even if had risk of 1% to be contagious try blood or whatever and as it did show is contagious it was a bit mistake to not be published everywhere so now need to test my self for all that things and let my gf known i could given this to her as well and be on stress every days if she has a bald patch...
i just post on your blog.Yyes disaster is very sad news that were old but not known at least to the world
And for all that didn't notice the number of alopecia universalis is on the rise i was in the town some day a go and saw 6 ppl before was hardly someone to be seen with that condition something is wrong and no one is doing a thing, even they think is there body doing it i am convinced after all i been try and all things i read so far that is not what they say it is
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