Polarized Type-1 Dendritic Cells (DC1) Producing High Levels of IL-12 Family Members Rescue Patient TH1-type Antimelanoma CD4+ T cell Responses In Vitro

2007 ◽  
Vol 30 (1) ◽  
pp. 75-82 ◽  
Author(s):  
Amy Wesa ◽  
Pawel Kalinski ◽  
John M. Kirkwood ◽  
Tomohide Tatsumi ◽  
Walter J. Storkus
Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3505-3513 ◽  
Author(s):  
Ralf Ignatius ◽  
Karsten Mahnke ◽  
Miguel Rivera ◽  
Keelung Hong ◽  
Frank Isdell ◽  
...  

Liposomes have been proposed as a vehicle to deliver proteins to antigen-presenting cells (APC), such as dendritic cells (DC), to stimulate strong T cell–mediated immune responses. Unfortunately, because of their instability in vivo and their rapid uptake by cells of the mononuclear phagocyte system on intravenous administration, most types of conventional liposomes lack clinical applicability. In contrast, sterically stabilized liposomes (SL) have increased in vivo stability. It is shown that both immature and mature DC take up SL into neutral or mildly acidic compartments distinct from endocytic vacuoles. These DC presented SL-encapsulated protein to both CD4+ and CD8+ T cells in vitro. Although CD4+ T-cell responses were comparable to those induced by soluble protein, CD8+ T-cell proliferation was up to 300-fold stronger when DC had been pulsed with SL-encapsulated ovalbumin. DC processed SL-encapsulated antigen through a TAP-dependent mechanism. Immunization of mice with SL-encapsulated ovalbumin led to antigen presentation by DC in vivo and stimulated greater CD8+ T-cell responses than immunization with soluble protein or with conventional or positively charged liposomes carrying ovalbumin. Therefore, the application of SL-encapsulated antigens offers a novel effective, safe vaccine approach if a combination of CD8+and CD4+ T-cell responses is desired (ie, in anti-viral or anti-tumor immunity).


2004 ◽  
Vol 27 (6) ◽  
pp. S34
Author(s):  
Amy Wesa ◽  
Pawel Kalinski ◽  
John M Kirkwood ◽  
Walter J Storkus

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3505-3513 ◽  
Author(s):  
Ralf Ignatius ◽  
Karsten Mahnke ◽  
Miguel Rivera ◽  
Keelung Hong ◽  
Frank Isdell ◽  
...  

Abstract Liposomes have been proposed as a vehicle to deliver proteins to antigen-presenting cells (APC), such as dendritic cells (DC), to stimulate strong T cell–mediated immune responses. Unfortunately, because of their instability in vivo and their rapid uptake by cells of the mononuclear phagocyte system on intravenous administration, most types of conventional liposomes lack clinical applicability. In contrast, sterically stabilized liposomes (SL) have increased in vivo stability. It is shown that both immature and mature DC take up SL into neutral or mildly acidic compartments distinct from endocytic vacuoles. These DC presented SL-encapsulated protein to both CD4+ and CD8+ T cells in vitro. Although CD4+ T-cell responses were comparable to those induced by soluble protein, CD8+ T-cell proliferation was up to 300-fold stronger when DC had been pulsed with SL-encapsulated ovalbumin. DC processed SL-encapsulated antigen through a TAP-dependent mechanism. Immunization of mice with SL-encapsulated ovalbumin led to antigen presentation by DC in vivo and stimulated greater CD8+ T-cell responses than immunization with soluble protein or with conventional or positively charged liposomes carrying ovalbumin. Therefore, the application of SL-encapsulated antigens offers a novel effective, safe vaccine approach if a combination of CD8+and CD4+ T-cell responses is desired (ie, in anti-viral or anti-tumor immunity).


2008 ◽  
Vol 82 (7) ◽  
pp. 3561-3573 ◽  
Author(s):  
Ellen R. Van Gulck ◽  
Guido Vanham ◽  
Leo Heyndrickx ◽  
Sandra Coppens ◽  
Katleen Vereecken ◽  
...  

ABSTRACT Developing an immunotherapy to keep human immunodeficiency virus type 1 (HIV-1) replication suppressed while discontinuing highly active antiretroviral therapy (HAART) is an important challenge. In the present work, we evaluated in vitro whether dendritic cells (DC) electroporated with gag mRNA can induce HIV-specific responses in T cells from chronically infected subjects. Monocyte-derived DC, from therapy-naïve and HAART-treated HIV-1-seropositive subjects, that were electroporated with consensus codon-optimized HxB2 gag mRNA efficiently expanded T cells, secreting gamma interferon (IFN-γ) and interleukin 2 (IL-2), as well as other cytokines and perforin, upon restimulation with a pool of overlapping Gag peptides. The functional expansion levels after 1 week of stimulation were comparable in T cells from HAART-treated and treatment-naïve patients and involved both CD4+ and CD8+ T cells, with evidence of bifunctionality in T cells. Epitope mapping of p24 showed that stimulated T cells had a broadened response toward previously nondescribed epitopes. DC, from HAART-treated subjects, that were electroporated with autologous proviral gag mRNA equally efficiently expanded HIV-specific T cells. Regulatory T cells did not prevent the induction of effector T cells in this system, whereas the blocking of PD-L1 slightly increased the induction of T-cell responses. This paper shows that DC, loaded with consensus or autologous gag mRNA, expand HIV-specific T-cell responses in vitro.


Virology ◽  
2009 ◽  
Vol 383 (2) ◽  
pp. 173-177 ◽  
Author(s):  
Angela Marzocchetti ◽  
Marco Lima ◽  
Troy Tompkins ◽  
Daniel.G. Kavanagh ◽  
Rajesh T. Gandhi ◽  
...  

Molecules ◽  
2016 ◽  
Vol 21 (7) ◽  
pp. 912 ◽  
Author(s):  
Chaitrali Saha ◽  
Mrinmoy Das ◽  
Emmanuel Stephen-Victor ◽  
Alain Friboulet ◽  
Jagadeesh Bayry ◽  
...  

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e86322 ◽  
Author(s):  
Verena Rombach-Riegraf ◽  
Anette C. Karle ◽  
Babette Wolf ◽  
Laetitia Sordé ◽  
Stephan Koepke ◽  
...  

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