Skip to main content

Overcoming CD4 deficiency to induce long-lived memory CD8+ CTL

One critical hurdle for therapeutic HIV vaccines is the deficiency of CD4+ T cell help during HIV infection. CD4+ T cell help has been shown to be necessary for induction of long-lived memory CD8+ cytotoxic T lymphocytes (CTL), and when CD8+ T cells are primed in its absence, they are susceptible to TRAIL-mediated death during secondary stimulation. We have found that IL-15 expression by a vaccine vector allowed induction of longer-lived, higher avidity memory CTL. We also observed that CD40L, a molecule by which helper T cells mediate help, induces dendritic cells to secrete IL-15. We therefore hypothesized that one mechanism by which CD4+ T helper cells induce longer-lived memory CTL may be to stimulate IL-15 production by the dendritic cell presenting antigen, and that therefore, IL-15 might overcome the need for CD4+ T cell help. We have now tested this hypothesis by demonstrating that immunization of CD4-depleted mice with a recombinant vaccinia-HIV vaccine vector expressing IL-15 induced long-lived memory CTL, whereas immunization of the depleted mice with a recombinant vaccinia-HIV vector not expressing IL-15 resulted in short-lived CTL that disappeared within two months. Further, CTL induced with the IL-15-expressing vaccine were resistant to TRAIL-mediated death on secondary stimulation, whereas those induced without IL-15 underwent apoptosis. Resistance was associated with upregulation by IL-15 of anti-apoptotic Bcl-XL and downregulation of Bax, a downstream transducer of the TRAIL death signal. These findings help explain the role of helper T cells in inducing long-lived memory CTL and provide a practical approach to overcome the deficiency of CD4+ T cell help during HIV infection for induction of CTL with a therapeutic vaccine for HIV, or with a vaccine for other opportunistic infections.

Author information



Corresponding author

Correspondence to Jay A Berzofsky.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Oh, S., Perera, L.P., Waldmann, T.A. et al. Overcoming CD4 deficiency to induce long-lived memory CD8+ CTL. Retrovirology 3, S17 (2006).

Download citation


  • Dendritic Cell
  • Therapeutic Vaccine
  • High Avidity
  • Vaccine Vector
  • Dendritic Cell Present Antigen