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10.1016/j.jaut.2016.11.001

http://scihub22266oqcxt.onion/10.1016/j.jaut.2016.11.001
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C6066671!6066671!27894837
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suck abstract from ncbi


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pmid27894837      J+Autoimmun 2017 ; 77 (ä): 76-88
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  • CD4+ Virtual Memory: Antigen-inexperienced T cells reside in the naïve, regulatory, and memory T cell compartments at similar frequencies, implications for autoimmunity #MMPMID27894837
  • Marusina AI; Ono Y; Merleev AA; Shimoda M; Ogawa H; Wang EA; Kondo K; Olney L; Luxardi G; Miyamura Y; Yilma TD; Villalobos IB; Bergstrom JW; Kronenberg DG; Soulika AM; Adamopoulos IE; Maverakis E
  • J Autoimmun 2017[Feb]; 77 (ä): 76-88 PMID27894837show ga
  • It is widely accepted that central and effector memory CD4+ T cells originate from naïve T cells after they have encountered their cognate antigen in the setting of appropriate co-stimulation. However, if this were true the diversity of T cell receptor (TCR) sequences within the naïve T cell compartment should be far greater than that of the memory T cell compartment, which is not supported by TCR sequencing data. Here we demonstrate that aged mice with far fewer naïve T cells, respond to the model antigen, hen eggwhite lysozyme (HEL), by utilizing the same TCR sequence as their younger counterparts. CD4+ T cell repertoire analysis of highly purified T cell populations from naïve animals revealed that the HEL-specific clones displayed effector and central ?memory? cell surface phenotypes even prior to having encountered their cognate antigen. Furthermore, HEL-inexperienced CD4+ T cells were found to reside within the naïve, regulatory, central memory, and effector memory T cell populations at similar frequencies and the majority of the CD4+ T cells within the regulatory and memory populations were unexpanded. These findings support a new paradigm for CD4+ T cell maturation in which a specific clone can undergo a differentiation process to exhibit a ?memory? or regulatory phenotype without having undergone a clonal expansion event. It also demonstrates that a foreign-specific T cell is just as likely to reside within the regulatory T cell compartment as it would the naïve compartment, arguing against the specificity of the regulatory T cell compartment being skewed towards self-reactive T cell clones. Finally, we demonstrate that the same set of foreign and autoreactive CD4+ T cell clones are repetitively generated throughout adulthood. The latter observation argues against T cell-depleting strategies or autologous stem cell transplantation as therapies for autoimmunity-as the immune system has the ability to regenerate pathogenic clones.
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