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Article: CD4+ T Cells from CD4C/HIVNef Transgenic Mice Show Enhanced Activation In Vivo with Impaired Proliferation In Vitro but Are Dispensable for the Development of a Severe AIDS-Like Organ Disease

TitleCD4<sup>+</sup> T Cells from CD4C/HIV<sup>Nef</sup> Transgenic Mice Show Enhanced Activation In Vivo with Impaired Proliferation In Vitro but Are Dispensable for the Development of a Severe AIDS-Like Organ Disease
Authors
Issue Date2004
Citation
Journal of Virology, 2004, v. 78, n. 10, p. 5244-5257 How to Cite?
AbstractThe cellular and molecular mechanisms of dysfunction and depletion of CD4+ T lymphocytes over the course of human immunodeficiency virus type 1 (HIV-1) infection are still incompletely understood, but chronic immune activation is thought to play an important role in disease progression. We studied CD4+ T-cell biology in CD4C/HIV transgenic (Tg) mice, in which Nef expression is sufficient to induce a severe AIDS-like disease including a preferential decrease of CD4+ T cells. We show here that Nef-expressing Tg CD4+ T cells exhibit an activated/memory-like phenotype which appears to be independent of antigenic stimulation, as documented in experiments involving breeding with AD10 TcR Tg mice. In addition, in vivo bromodeoxyuridine incorporation showed that a larger proportion of Tg than non-Tg CD4+ T cells entered the S phase. However, in vitro, Tg CD4+ T cells were found to have a very limited capacity to divide in response to stimulation with anti-CD3 and anti-CD28 or in allogeneic mixed leukocyte reactions. Interestingly, despite these observations, the deletion of Tg CD4+ T cells had little impact on the development of other AIDS-like organ phenotypes. Thus, the Nef-induced chronic activation of CD4 + T cells may exhaust the T-cell pool and may contribute to the thymic atrophy and the low number of CD4+ T cells observed in these Tg mice.
Persistent Identifierhttp://hdl.handle.net/10722/291742
ISSN
2023 Impact Factor: 4.0
2023 SCImago Journal Rankings: 1.378
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWeng, Xiaoduan-
dc.contributor.authorPriceputu, Elena-
dc.contributor.authorChrobak, Pavel-
dc.contributor.authorPoudrier, Johanne-
dc.contributor.authorKay, Denis G.-
dc.contributor.authorHanna, Zaher-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorJolicoeur, Paul-
dc.date.accessioned2020-11-17T14:55:01Z-
dc.date.available2020-11-17T14:55:01Z-
dc.date.issued2004-
dc.identifier.citationJournal of Virology, 2004, v. 78, n. 10, p. 5244-5257-
dc.identifier.issn0022-538X-
dc.identifier.urihttp://hdl.handle.net/10722/291742-
dc.description.abstractThe cellular and molecular mechanisms of dysfunction and depletion of CD4+ T lymphocytes over the course of human immunodeficiency virus type 1 (HIV-1) infection are still incompletely understood, but chronic immune activation is thought to play an important role in disease progression. We studied CD4+ T-cell biology in CD4C/HIV transgenic (Tg) mice, in which Nef expression is sufficient to induce a severe AIDS-like disease including a preferential decrease of CD4+ T cells. We show here that Nef-expressing Tg CD4+ T cells exhibit an activated/memory-like phenotype which appears to be independent of antigenic stimulation, as documented in experiments involving breeding with AD10 TcR Tg mice. In addition, in vivo bromodeoxyuridine incorporation showed that a larger proportion of Tg than non-Tg CD4+ T cells entered the S phase. However, in vitro, Tg CD4+ T cells were found to have a very limited capacity to divide in response to stimulation with anti-CD3 and anti-CD28 or in allogeneic mixed leukocyte reactions. Interestingly, despite these observations, the deletion of Tg CD4+ T cells had little impact on the development of other AIDS-like organ phenotypes. Thus, the Nef-induced chronic activation of CD4 + T cells may exhaust the T-cell pool and may contribute to the thymic atrophy and the low number of CD4+ T cells observed in these Tg mice.-
dc.languageeng-
dc.relation.ispartofJournal of Virology-
dc.titleCD4<sup>+</sup> T Cells from CD4C/HIV<sup>Nef</sup> Transgenic Mice Show Enhanced Activation In Vivo with Impaired Proliferation In Vitro but Are Dispensable for the Development of a Severe AIDS-Like Organ Disease-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1128/JVI.78.10.5244-5257.2004-
dc.identifier.pmid15113906-
dc.identifier.pmcidPMC400335-
dc.identifier.scopuseid_2-s2.0-2342569732-
dc.identifier.volume78-
dc.identifier.issue10-
dc.identifier.spage5244-
dc.identifier.epage5257-
dc.identifier.isiWOS:000221212100032-
dc.identifier.issnl0022-538X-

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