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

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 x 10(10) 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.