Interleukin-7-treated naive T cells can be productively infected by T-cell-adapted and primary isolates of human immunodeficiency virus 1

Although human Immunodeficiency virus (HIV) gag/pol DNA can be detected In naive T cells, whether naive T cells can be productively Infected by HIV is still questionable. Given that Interleukin-7 (IL-7) Is a prospective therapeutic Immunomodulator for the treatment of HIV, we evaluated the effect of IL-7 on promoting naive T-cell Infection of laboratory-adapted (iIIB), M-tropic, and primary Isolates of HIV. Initially, we determined that the 3 cell surface markers widely used to Identity naive T cells (CD45RA(+)CD45RO(-), CD45RA(+)CD62L(+), and CD45RO(-)CD27(+)CD95(low)) are all equivalent in T-cell receptor excision circle content, a marker for the replicative history of a cell as well as for de novo T cells. We therefore used CD45RA+CD45RO- expression to define naive T cells in this study. We demonstrate that although untreated or IL-2-treated naive T cells are not productively infected by HIV, IL-7 pretreatment mediated the productive Infection of laboratory-adapted, M-tropic, and primary Isolates of HIV as determined by p24 core antigen production. This up-regulation was between 8- and 58-fold, depending on the HIV isolate used. IL-7 pretreatment of naive T cells also potently up-regulated surface expression of CXCR4 but not CCR5 and mediated the expansion of naive T cells without the acquisition of the primed CD45RO phenotype. Collectively, these data Indicate that IL-7 augments naive T-cell susceptibility to HIV and that under the appropriate environmental milieu, naive T cells may be a source of HIV productive Infection. This Information needs to be considered in evaluating IL-7 as an Immunomodulator for HIV-infected patients. (C) 2002 by The American Society of Hematology.