{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Leone A"],"funding":["NIDCR NIH HHS","NCRR NIH HHS","NIAID NIH HHS"],"pagination":["1650-9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3050806"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["185(3)"],"pubmed_abstract":["CD4(+) T cell depletion is a fundamental component of HIV infection and AIDS pathogenesis and is not always reversed following antiretroviral therapy (ART). In this study, the SIV-infected rhesus macaque model was used to assess recombinant simian IL-7 in its glycosylated form (rsIL-7gly) to enhance regeneration of CD4(+) T cells, particularly the crucial central memory compartment, after ART. We assessed the impact of rsIL-7gly administration as single injections and as a cluster of three doses. Irrespective of the dosing strategy used, the rsIL-7gly administration transiently increased proliferation of both central memory and naive cells, in both CD4(+) and CD8(+) subsets, without increasing SIV levels in the blood. Administration of rsIL-7gly at intervals of 4-6 wk maximized the proliferative response to therapy but resulted in only transient increases in peripheral blood T cell counts. Although more frequent rsIL-7gly \"clustered\" dosing (three times weekly with 2 wk of rest and then repeat) induced only an initial proliferative burst by CD4(+) T cells, this dosing strategy resulted in sustained increases in peripheral blood CD4(+) T cell counts. The clustered rsIL-7gly treatment regimen was shown to increase the half-life of a BrdU label among memory T cells in the blood when compared with that of macaques treated with ART alone, which is consistent with enhanced cell survival. These results indicate that dosing intervals have a major impact on the response to rsIL-7gly in SIV-positive ART-treated rhesus macaques and that optimum dosing strategies may be ones that induce CD4(+) T cell proliferation initially and provide increased CD4(+) T cell survival."],"journal":["Journal of immunology (Baltimore, Md. : 1950)"],"pubmed_title":["Increased CD4+ T cell levels during IL-7 administration of antiretroviral therapy-treated simian immunodeficiency virus-positive macaques are not dependent on strong proliferative responses."],"pmcid":["PMC3050806"],"funding_grant_id":["R01 AI035522","R01 DE017541-05","R37 AI054292","R01-DE017541","R01-AI035522","R01 AI035522-10","P51-RR00163","R01 DE017541","P51 RR000163","R37-AI054292"],"pubmed_authors":["Piatak M","Picker LJ","Lifson JD","Assouline B","Axthelm MK","Morre M","Okoye A","Rohankhedkar M","Legasse A","Leone A","Sodora DL","Villinger F"],"additional_accession":[]},"is_claimable":false,"name":"Increased CD4+ T cell levels during IL-7 administration of antiretroviral therapy-treated simian immunodeficiency virus-positive macaques are not dependent on strong proliferative responses.","description":"CD4(+) T cell depletion is a fundamental component of HIV infection and AIDS pathogenesis and is not always reversed following antiretroviral therapy (ART). In this study, the SIV-infected rhesus macaque model was used to assess recombinant simian IL-7 in its glycosylated form (rsIL-7gly) to enhance regeneration of CD4(+) T cells, particularly the crucial central memory compartment, after ART. We assessed the impact of rsIL-7gly administration as single injections and as a cluster of three doses. Irrespective of the dosing strategy used, the rsIL-7gly administration transiently increased proliferation of both central memory and naive cells, in both CD4(+) and CD8(+) subsets, without increasing SIV levels in the blood. Administration of rsIL-7gly at intervals of 4-6 wk maximized the proliferative response to therapy but resulted in only transient increases in peripheral blood T cell counts. Although more frequent rsIL-7gly \"clustered\" dosing (three times weekly with 2 wk of rest and then repeat) induced only an initial proliferative burst by CD4(+) T cells, this dosing strategy resulted in sustained increases in peripheral blood CD4(+) T cell counts. The clustered rsIL-7gly treatment regimen was shown to increase the half-life of a BrdU label among memory T cells in the blood when compared with that of macaques treated with ART alone, which is consistent with enhanced cell survival. These results indicate that dosing intervals have a major impact on the response to rsIL-7gly in SIV-positive ART-treated rhesus macaques and that optimum dosing strategies may be ones that induce CD4(+) T cell proliferation initially and provide increased CD4(+) T cell survival.","dates":{"release":"2010-01-01T00:00:00Z","publication":"2010 Aug","modification":"2020-10-31T08:29:22Z","creation":"2019-03-26T23:42:53Z"},"accession":"S-EPMC3050806","cross_references":{"pubmed":["20622118"],"doi":["10.4049/jimmunol.0902626"]}}