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 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.
Levine
Bruce L
BL
Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania, USA. levinebl@mail.med.upennn.edu
Bernstein
Wendy B
WB
Aronson
Naomi E
NE
Schlienger
Katia
K
Cotte
Julio
J
Perfetto
Steven
S
Humphries
Mary J
MJ
Ratto-Kim
Silvia
S
Birx
Deborah L
DL
Steffens
Carolyn
C
Landay
Alan
A
Carroll
Richard G
RG
June
Carl H
CH
D019264:Adoptive Transfer; D000328:Adult; D001781:Blood Component Removal; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation*; D005240:Feasibility Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology*; D014182:Transplantation, Autologous
D019713:Receptors, CCR5