Immune reconstitution following autologous transfers of CD3/CD28 stimulated CD4+ T cells to HIV-infected persons

Wendy B. Bernstein, Josephine H. Cox, Naomi E. Aronson, Laree Tracy, Katia Schlienger, Silvia Ratto-Kim, Robin Garner, Julio Cotte, Zhaohui Zheng, Lena Winestone, Caroline Liebig, Lynee M. Galley, Mark Connors, Deborah L. Birx, Richard G. Carroll, Bruce L. Levine*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

We have previously shown that adoptive transfer of in vitro CD3/CD28 activated autologous CD4+ T cells results in increased CD4 counts and CD4/CD8 ratios in HIV+ subjects. In this report, analysis of variable beta (Vβ) chain T cell receptor (TCR) repertoire showed that CD3/CD28 stimulation was able to increase polyclonality within skewed spectra types in vitro. In vivo, two of eight subjects showed increase in TCR diversity and importantly, in no subject did a highly skewed in vivo repertoire emerge. Measurement of proliferative response to alloantigen showed increases following infusions. Response to pharmacological stimulus and lectin via Interferon-γ ELISpot assay showed increases in a subset of subjects following infusions. However, interferon-γ response to HIV antigens and peptides declined concurrent with stable or diminishing latent infectious viral load in CD4+ T cells. These data provide further evidence that adoptive transfer of activated autologous CD4+ T cells can augment the immune system.

Original languageEnglish
Pages (from-to)262-274
Number of pages13
JournalClinical Immunology
Volume111
Issue number3
DOIs
StatePublished - Jun 2004
Externally publishedYes

Keywords

  • Adoptive transfer
  • CD28
  • ELISpot
  • HIV
  • Immune reconstitution
  • Immunotherapy
  • TCR V beta

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