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Article: CD4 T cells, lymphopenia, and IL-7 in a multistep pathway to autoimmunity

TitleCD4 T cells, lymphopenia, and IL-7 in a multistep pathway to autoimmunity
Authors
KeywordsLymphocyte homeostasis
Dendritic cells
Cytokines
CD8 T cells
Cyclophosphamide
Issue Date2008
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2008, v. 105, n. 8, p. 2999-3004 How to Cite?
AbstractThere are many inhibitory mechanisms that function at the cellular and molecular levels to maintain tolerance. Despite this, self-reactive clones escape regulatory mechanisms and cause autoimmunity in certain circumstances. We hypothesized that the same mechanisms that permit T cells to expand during homeostatic proliferation may inadvertently promote autoimmunity under certain conditions. One major homeostatic cytokine is IL-7, and studies have linked it or its receptor to the development of multiple sclerosis and other autoimmune diseases. We show in a model of β-islet cell self-reactivity that the transfer of activated autoreactive CD4 T cells can prime and expand endogenous autoreactive CD8 T cells in a CD28- and CD40-dependent manner through the licensing of dendritic cells. Despite this, mice do not develop diabetes. However, the provision of exogenous IL-7 or the physiological production of IL-7 associated with lymphopenia was able to profoundly promote the expansion of self-reactive clones even in the presence of regulatory T cells. Autoimmune diabetes rapidly ensued with CD4 help and the subsequent activation of CD8 T cells, which contributed to disease progression. With the advent of many biologicals targeting TNFα, IL-6, and IL-1 and their effective use in the treatment of autoimmune diseases, we propose that IL-7 and its receptor may be promising targets for biological agents in the treatment of autoimmunity. © 2008 by The National Academy of Sciences of the USA.
Persistent Identifierhttp://hdl.handle.net/10722/291820
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCalzascia, Thomas-
dc.contributor.authorPellegrini, Marc-
dc.contributor.authorLin, Albert-
dc.contributor.authorGarza, Kristine M.-
dc.contributor.authorElford, Alisha R.-
dc.contributor.authorShahinian, Arda-
dc.contributor.authorOhashi, Pamela S.-
dc.contributor.authorMak, Tak W.-
dc.date.accessioned2020-11-17T14:55:11Z-
dc.date.available2020-11-17T14:55:11Z-
dc.date.issued2008-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2008, v. 105, n. 8, p. 2999-3004-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/291820-
dc.description.abstractThere are many inhibitory mechanisms that function at the cellular and molecular levels to maintain tolerance. Despite this, self-reactive clones escape regulatory mechanisms and cause autoimmunity in certain circumstances. We hypothesized that the same mechanisms that permit T cells to expand during homeostatic proliferation may inadvertently promote autoimmunity under certain conditions. One major homeostatic cytokine is IL-7, and studies have linked it or its receptor to the development of multiple sclerosis and other autoimmune diseases. We show in a model of β-islet cell self-reactivity that the transfer of activated autoreactive CD4 T cells can prime and expand endogenous autoreactive CD8 T cells in a CD28- and CD40-dependent manner through the licensing of dendritic cells. Despite this, mice do not develop diabetes. However, the provision of exogenous IL-7 or the physiological production of IL-7 associated with lymphopenia was able to profoundly promote the expansion of self-reactive clones even in the presence of regulatory T cells. Autoimmune diabetes rapidly ensued with CD4 help and the subsequent activation of CD8 T cells, which contributed to disease progression. With the advent of many biologicals targeting TNFα, IL-6, and IL-1 and their effective use in the treatment of autoimmune diseases, we propose that IL-7 and its receptor may be promising targets for biological agents in the treatment of autoimmunity. © 2008 by The National Academy of Sciences of the USA.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.subjectLymphocyte homeostasis-
dc.subjectDendritic cells-
dc.subjectCytokines-
dc.subjectCD8 T cells-
dc.subjectCyclophosphamide-
dc.titleCD4 T cells, lymphopenia, and IL-7 in a multistep pathway to autoimmunity-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.0712135105-
dc.identifier.pmid18287017-
dc.identifier.pmcidPMC2268574-
dc.identifier.scopuseid_2-s2.0-42949131224-
dc.identifier.volume105-
dc.identifier.issue8-
dc.identifier.spage2999-
dc.identifier.epage3004-
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000253567900046-
dc.identifier.issnl0027-8424-

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