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 identify 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.
Steffens
Carolyn M
CM
Department of Immunology/Microbiology at Rush-Presbyterian-St Luke's Medical Center, Rush University, Chicago, IL 60612, USA.
Managlia
Elizabeth Z
EZ
Landay
Alan
A
Al-Harthi
Lena
L
D015658:HIV Infections / Q000139:chemically induced; D015497:HIV-1 / Q000254:growth & development* / Q000472:pathogenicity; D006801:Humans; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000494:pharmacology*; D017493:Leukocyte Common Antigens; D019713:Receptors, CCR5 / Q000187:drug effects / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D014775:Virus Activation / Q000187:drug effects
D015851:Interleukin-7; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D017493:Leukocyte Common Antigens