Adoptive transfer of costimulated CD4+ T cells induces expansion of peripheral T cells and decreased CCR5 expression in HIV infection

Bruce L. Levine, Wendy B. Bernstein, Naomi E. Aronson, Katia Schlienger, Julio Cotte, Steven Perfetto, Mary J. Humphries, Silvia Ratto-Kim, Deborah L. Birx, Carolyn Steffens, Alan Landay, Richard G. Carroll, Carl H. June

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

Abstract

To study the safety and feasibility of T-cell reconstitution in HIV-infected individuals, we adoptively transferred activated autologous CD4+ T cells. Polyclonal peripheral blood CD4+ cells were costimulated ex vivo and subjects were given infusions of up to 3 × 1010 activated CD4+ cells. Dose-dependent increases in CD4+ cell counts and in the CD4:CD8 ratio were observed. Sustained increases in the fraction of cytokine-secreting T cells and decreases in the percentage of CD4+CCR5+ cells were noted in vivo, suggesting enhanced function and resistance to HIV infection. The frequency of CD4+Ki-67+ cells increased whereas CD4+ T cells containing T cell-receptor rearrangement excision circles (TRECs) decreased. These findings indicate that expansion of the peripheral T-cell pool mediated the increase in CD4 counts and suggest that approaches to reconstitute CD4 helper cell activity and decrease CCR5 expression may augment natural immunity to HIV infection.

Original languageEnglish
Pages (from-to)47-53
Number of pages7
JournalNature Medicine
Volume8
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

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