Increased CD4+ T cell levels during IL-7 administration of ART treated SIV+ macaques are not dependent on strong proliferative responses

• Published in: The Journal of immunology (1950) 2010-07, Vol.185 (3), p.1650-1659
• Main Authors: Leone, Amanda, Rohankhedkhar, Mukta, Okoye, Afam, Legasse, Alfred, Axthelm, Michael K., Villinger, Francois, Piatak, Michael, Lifson, Jeffrey D., Assouline, Brigitte, Morre, Michel, Picker, Louis J., Sodora, Donald L.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0902626

CD4+ T cell depletion is a fundamental component of HIV infection and AIDS pathogenesis, and is not always reversed following anti-retroviral therapy (ART). Here the SIV-infected Rhesus macaque model was utilized to assess recombinant simian IL-7 in its glycosylated form (rsIL-7gly) to enhance regeneration of CD4+ T cells, particularly the crucial central memory (CM) compartment, post ART. We assessed the impact of rsIL-7gly administration as single injections and as a cluster of three doses. Irrespective of the dosing strategy utilized, the rsIL-7gly administration transiently increased proliferation of both CM and naïve cells, in both CD4+ and CD8+ subsets without increasing SIV levels in the blood. Administration of rsIL-7gly at intervals of 4-6 weeks maximized the proliferative response to therapy, but resulted in only transient increases in peripheral blood T cell counts. However, more frequent rsIL-7gly ‘clustered’ dosing (weekly × 3, with 2 weeks 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 bromodeoxy-uridine (BrDU) label among memory T cells in the blood when compared to macaques treated with ART alone, consistent with enhanced cell survival. These results indicate that dosing intervals have a major impact on the response to rsIL-7gly in SIV+ ART treated RM, and that optimum dosing strategies may be ones that induce CD4+ T cell proliferation initially and provide increased CD4+ T cell survival.