Efficient stimulation of HIV-1-specific T cells using dendritic cells electroporated with mRNA encoding autologous HIV-1 Gag and Env proteins.
Infection with human immunodeficiency virus type 1 (HIV-1) is characterized by dysfunction of HIV-1-specific T cells. To control the virus, antigen-loaded dendritic cells (DCs) might be useful to boost and broaden HIV-specific T-cell responses. In the present study, monocyte-derived DCs from nontreated HIV-1-seropositive patients were electroporated with codon-optimized ("humanized") mRNA encoding consensus HxB-2 (hHXB-2) Gag protein. These DCs elicited a strong HIV-1 Gag-specific interferon-gamma (IFN-gamma) response by an HLA-A2-restricted CD8+ T-cell line. Moreover, hHXB-2 gag mRNA-electroporated DCs also triggered IFN-gamma secretion by autologous peripheral blood mononuclear cells (PBMCs), CD4+ T cells, and CD8+ T cells from all patients tested. Next, a novel strategy was developed using autologous virus sequences. Significant specific IFN-gamma T-cell responses were induced in all patients tested by DCs electroporated with patients' autologous polymerase chain reaction (PCR)-amplified and in vitro-transcribed proviral and plasma viral mRNA encoding either Gag or Env. The stimulatory effect was seen on PBMCs, CD8+ T cells, and CD4+ T cells, demonstrating both major histocompatibility complex (MHC) class I and MHC class II antigen presentation. Moreover, a significant interleukin-2 (IL-2) T-cell response was induced by DCs electroporated with hHxB-2 or proviral gag mRNA. These findings open a major perspective for the development of patient-specific immunotherapy for HIV-1 disease.
Van Gulck
Ellen R A
ER
HIV and Retrovirology Research Unit, Department of Microbiology, Institute of Tropical Medicine of Antwerp, Nationalestraat 155, 2000 Antwerp, Belgium. evangulck@itg.be
Ponsaerts
Peter
P
Heyndrickx
Leo
L
Vereecken
Katleen
K
Moerman
Filip
F
De Roo
Ann
A
Colebunders
Robert
R
Van den Bosch
Glenn
G
Van Bockstaele
Dirk R
DR
Van Tendeloo
Viggo F I
VF
Allard
Sabine
S
Verrier
Bernard
B
Marañón
Concepción
C
Hoeffel
Guillaume
G
Hosmalin
Anne
A
Berneman
Zwi N
ZN
Vanham
Guido
G
D019264:Adoptive Transfer / Q000379:methods; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D018274:Electroporation; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology* / Q000628:therapy; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology; D014182:Transplantation, Autologous; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D015683:Gene Products, gag; D006023:Glycoproteins; D015789:HLA-A2 Antigen; D012367:RNA, Viral; D014759:Viral Envelope Proteins; C445079:envelope protein, Feline immunodeficiency virus; D007371:Interferon-gamma