Expansion of polyfunctional HIV-specific T cells upon stimulation with mRNA electroporated dendritic cells in the presence of immunomodulatory drugs

J Virol. 2012 Sep;86(17):9351-60. doi: 10.1128/JVI.00472-12. Epub 2012 Jun 20.


Recently, it has been demonstrated that disease progression during HIV infection is not determined merely by the number of HIV-specific T cells but also by their quality (J. R. Almeida, et al., J. Exp. Med. 204:2473-2485, 2007; C. T. Berger, et al., J. Virol. 85:9334-9345, 2011; M. R. Betts, et al., Blood 107:4781-4789, 2006; V. V. Ganusov, et al., J. Virol. 85:10518-10528, 2011; P. Kiepiela, et al., Nat. Med. 13:46-53, 2007; and F. Pereyra, et al., J. Infect. Dis. 197:563-571, 2008). Therefore, strategies to specifically enhance or induce high-quality, HIV-specific T-cell responses are necessary to develop effective immune therapies. Thalidomide, lenalidomide, and pomalidomide have a strong capacity to boost immune responses and are therefore referred to as immunomodulatory drugs (IMiDs). We evaluated the effects of lenalidomide and pomalidomide on HIV-specific T cells. We found that the presence of IMiDs during in vitro T-cell stimulation with dendritic cells electroporated with Gag- or Nef-encoding mRNA resulted in higher numbers of cytokine-secreting HIV-specific CD8(+) T cells, particularly inducing polyfunctional HIV-specific CD8(+) T cells with an enhanced lytic capacity. Furthermore, CD8(+) T-cell responses were detected upon stimulation with lower antigenic peptide concentrations, and a higher number of Gag epitopes was recognized upon addition of IMiDs. Finally, IMiDs reduced the proliferation of the HIV-specific CD4(+) T cells while increasing the number of polyfunctional CD4(+) T cells. These results provide new information about the effects of IMiDs on antigen-specific T cells and suggest that these drugs increase the efficacy of immune therapies for infectious diseases and cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / virology*
  • Electroporation
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • HIV-1 / immunology
  • Humans
  • Immunologic Factors / pharmacology*
  • Lenalidomide
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Species Specificity
  • Thalidomide / analogs & derivatives
  • Thalidomide / pharmacology
  • gag Gene Products, Human Immunodeficiency Virus / genetics
  • gag Gene Products, Human Immunodeficiency Virus / immunology
  • nef Gene Products, Human Immunodeficiency Virus / genetics
  • nef Gene Products, Human Immunodeficiency Virus / immunology


  • Immunologic Factors
  • RNA, Messenger
  • gag Gene Products, Human Immunodeficiency Virus
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1
  • Thalidomide
  • pomalidomide
  • Lenalidomide