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Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
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Simultaneous activation of viral antigen-specific memory CD4+ and CD8+ T-cells using mRNA-electroporated

Glenn A Van den Bosch1, Ellen Van Gulck, Peter Ponsaerts

  • 1Laboratory of Experimental Hematology, Antwerp University (UA), Antwerp University Hospital (UZA), Wilrijkstraat 10, 2650 Edegem, Belgium.

Journal of Immunotherapy (Hagerstown, Md. : 1997)
|September 15, 2006
PubMed

Insights

This study shows that mRNA-electroporated CD40-activated B cells can simultaneously reactivate both CD4 and CD8 T-cells. This approach shows potential for cellular immunotherapy against cytomegalovirus (CMV) and human immunodeficiency virus (HIV) infections.

Area of Science:

  • Immunology
  • Cellular Immunology
  • Vaccinology

Background:

  • Effective cellular immunity requires both CD4 and CD8 T-cells.
  • Cytomegalovirus (CMV) and human immunodeficiency virus (HIV) infections pose significant clinical challenges.
  • Existing T-cell reactivation strategies have limitations.

Purpose of the Study:

  • To develop a method for simultaneously reactivating viral antigen-specific memory CD4 and CD8 T-cells.
  • To investigate the use of mRNA-electroporated autologous CD40-activated B cells for this purpose.
  • To assess the feasibility of this approach in CMV- and HIV-seropositive individuals.

Main Methods:

  • CD40-activated B cells were cultured from CMV- and HIV-seropositive subjects.
  • Cells were electroporated with mRNA encoding viral antigens (HIV gag or CMV pp65).
  • Reactivation of antigen-specific CD4 and CD8 T-cells was assessed by measuring cytokine production and phenotype.

Main Results:

  • HIV-1 gag mRNA-electroporated CD40-B cells expressed and secreted HIV p24 antigen.
  • These cells reactivated Gag-specific interferon-gamma-producing CD4 and CD8 T-cells in vitro.
  • CMV pp65 mRNA-transfected CD40-B cells induced CMV-specific CD4 and CD8 T-cells with effector memory phenotype and IL-2 production.

Conclusions:

  • Simultaneous activation of CD4 and CD8 T-cells using mRNA-electroporated CD40-B cells is feasible in CMV and HIV-1-seropositive individuals.
  • This strategy holds promise for cellular immunotherapy of infectious diseases.
  • The approach effectively generates antigen-specific T-cell responses crucial for long-lasting immunity.

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