Increased CD4+ T cell levels during IL-7 administration of antiretroviral therapy-treated simian immunodeficiency virus-positive macaques are not dependent on …

A Leone, M Rohankhedkar, A Okoye… - The Journal of …, 2010 - journals.aai.org
A Leone, M Rohankhedkar, A Okoye, A Legasse, MK Axthelm, F Villinger, M Piatak…
The Journal of Immunology, 2010journals.aai.org
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 …
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.
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