TY - JOUR
T1 - Protective CD8+ T-cell responses to cytomegalovirus driven by rAAV/GFP/ IE1 loading of dendritic cells
AU - Yu, Yuefei
AU - Pilgrim, Petra
AU - Yan, Juqiang
AU - Zhou, Wei
AU - Jenkins, Marjorie
AU - Gagliano, Nicoletta
AU - Bumm, Klaus
AU - Cannon, Martin
AU - Milzani, Aldo
AU - Dalle-Donne, Isabella
AU - Martin, W. Martin
AU - Cobos, Everardo
AU - Chiriva-Internati, Maurizio
N1 - Funding Information:
This project was supported by the Institutional Research Program of the Texas Tech University Health Sciences Center, the Southwest Cancer Treatment and Research Center Program, the Laura W. Bush Institute for Women's Health and Center for Women's Health and Gender-Based Medicine, Texas Tech University Health Sciences Center. Cardiovascular TTUHSC Seed Grant.
PY - 2008/10/5
Y1 - 2008/10/5
N2 - Background: Recent studies demonstrate that recombinant adeno-associated virus (rAAV)-based antigen loading of dendritic cells (DCs) generates in vitro, significant and rapid cytotoxic T-lymphocyte (CTL) responses against viral antigens. Methods: We used the rAAV system to induce specific CTLs against CVM antigens for the development of cytomegalovirus HCMV) gene therapy. As an extension of the versatility of the rAAV system, we incorporated immediate-early 1 (IE1), expressed in HCMV. Our rAAV vector induced a strong stimulation of CTLs directed against the HCMV antigen IE1. We then investigated the efficiency of the CTLs in killing IE1 targeted cells. Results: A significant MHC Class I-restricted, anti-IE1-specificCTL killing was demonstrated against IE1 positive peripheral blood mononuclear cells (PBMC) after one, in vitro, stimulation. Conclusion: In summary, single PBMC stimulation with rAAV/IE1 pulsed DCs induces strong antigen specific-CTL generation. CTLs were capable to lyse low doses of peptides pulsed into target cells. These data suggest that AAV-based antigen loading of DCs is highly effective for generating human CTL responses against HCMV antigens.
AB - Background: Recent studies demonstrate that recombinant adeno-associated virus (rAAV)-based antigen loading of dendritic cells (DCs) generates in vitro, significant and rapid cytotoxic T-lymphocyte (CTL) responses against viral antigens. Methods: We used the rAAV system to induce specific CTLs against CVM antigens for the development of cytomegalovirus HCMV) gene therapy. As an extension of the versatility of the rAAV system, we incorporated immediate-early 1 (IE1), expressed in HCMV. Our rAAV vector induced a strong stimulation of CTLs directed against the HCMV antigen IE1. We then investigated the efficiency of the CTLs in killing IE1 targeted cells. Results: A significant MHC Class I-restricted, anti-IE1-specificCTL killing was demonstrated against IE1 positive peripheral blood mononuclear cells (PBMC) after one, in vitro, stimulation. Conclusion: In summary, single PBMC stimulation with rAAV/IE1 pulsed DCs induces strong antigen specific-CTL generation. CTLs were capable to lyse low doses of peptides pulsed into target cells. These data suggest that AAV-based antigen loading of DCs is highly effective for generating human CTL responses against HCMV antigens.
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U2 - 10.1186/1479-5876-6-56
DO - 10.1186/1479-5876-6-56
M3 - Article
C2 - 18834548
AN - SCOPUS:54549121610
SN - 1479-5876
VL - 6
JO - Journal of translational medicine
JF - Journal of translational medicine
M1 - 56
ER -