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.
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Acknowledgements
We thank T. Francomano, C. Small, D. Ritchey, D. Kim, D. Kim, G. McCrary, B. Gregson, Z. Zheng, B. Hudson and H. Flaks for technical support; J.L. Riley, M.T. Vahey and L.L. Jagodzinski for laboratory assistance; T. Baradet for immunohistochemistry; D. Van Epps for support and reagents; K.F. Wagner, D.L. Mayers and D.S. Burke for their initial support and encouragement; and the patients and staff of the Henry M. Jackson Foundation Special Immunology Clinic and the Walter Reed Army Medical Center Infectious Diseases Clinic for their participation in and commitment to this clinical trial. This work was supported by Army contract DAMD17-93-V-3004, the Henry M. Jackson Foundation and the Leonard and Madlyn Abramson Family Cancer Research Institute. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Army, Navy, Department of Defense or US Government.
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Levine, B., Bernstein, W., Aronson, N. et al. Adoptive transfer of costimulated CD4+ T cells induces expansion of peripheral T cells and decreased CCR5 expression in HIV infection. Nat Med 8, 47–53 (2002). https://doi.org/10.1038/nm0102-47
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DOI: https://doi.org/10.1038/nm0102-47
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