Published online before print August 24, 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department of Medicine, University of California San Diego, La Jolla, California, USA; and VA San Diego Healthcare System, San Diego, California, USA
1 Correspondence: Department of Medicine, Stein Clinical Sciences Bldg., Room 304, University of California San Diego, 9500 Gilman Dr., #0679, La Jolla, CA 92093-0679, USA. E-mail: rkornbluth{at}ucsd.edu
Agents that activate dendritic cells are essential components for vaccines and can be conceptualized as molecular adjuvants. Other molecular adjuvants affect downstream factors that shape the resulting immune response. This review provides a compendium of recently studied molecular adjuvants, focusing on CD8+ T cell responses, which have important roles in HIV vaccines. Reference is also made to CD8+ T cell antitumor responses, where parallel studies of molecular adjuvants are being pursued. Molecular adjuvants can be considered in the following groups: TNF superfamily molecules such as CD40 ligand; agonists for TLRs; agonists for NAIP, CIITA, HET-E, TP-1-leucine-rich repeat pathway receptors, such as nucleotide-binding and oligomerization domain (NOD)1, NOD2, and cryopyrin; chemokines; ILs; CSFs; IFNs; alarmins; and purinergic P2X7 receptor agonists. Complementing these positively acting agents are strategies to reduce the immunosuppressive effects of CD4+CD25+ regulatory T cells and negatively acting factors such as TGF-ß, IL-10, suppressor of cytokine signaling 1, and programmed cell death-1 using neutralizing antibodies, antisense, and small interfering RNA. Especially effective are combinations of molecular adjuvants, which can elicit a massive expansion of antigen-specific CD8+ T cells and show unprecedented efficacy in vaccine and tumor models. Taken together, these new approaches provide significant incremental progress in the development of vaccines to elicit cell-mediated immunity against HIV and other pathogens.
Key Words: dendritic cells • monocyte/macrophages • T cells • CD40 • TLR • regulatory T cells
This article has been cited by other articles:
 |
|
 |
|
  M. McCarron and D. J. Reen Activated Human Neonatal CD8+ T Cells Are Subject to Immunomodulation by Direct TLR2 or TLR5 Stimulation J. Immunol., January 1, 2009; 182(1): 55 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Schachter, A. P. Motta, A. de Souza Zamorano, H. A. da Silva-Souza, M. Z. P. Guimaraes, and P. M. Persechini ATP-induced P2X7-associated uptake of large molecules involves distinct mechanisms for cations and anions in macrophages J. Cell Sci., October 1, 2008; 121(19): 3261 - 3270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Wells, C. J. Cowled, F. Farzaneh, and A. Noble Combined Triggering of Dendritic Cell Receptors Results in Synergistic Activation and Potent Cytotoxic Immunity J. Immunol., September 1, 2008; 181(5): 3422 - 3431. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Ahonen, A. Wasiuk, S. Fuse, M. J. Turk, M. S. Ernstoff, A. A. Suriawinata, J. D. Gorham, R. M. Kedl, E. J. Usherwood, and R. J. Noelle Enhanced efficacy and reduced toxicity of multifactorial adjuvants compared with unitary adjuvants as cancer vaccines Blood, March 15, 2008; 111(6): 3116 - 3125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Triccas, E. Shklovskaya, J. Spratt, A. A. Ryan, U. Palendira, B. Fazekas de StGroth, and W. J. Britton Effects of DNA- and Mycobacterium bovis BCG-Based Delivery of the Flt3 Ligand on Protective Immunity to Mycobacterium tuberculosis Infect. Immun., November 1, 2007; 75(11): 5368 - 5375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Montaner, S. M. Crowe, S. Aquaro, C.-F. Perno, M. Stevenson, and R. G. Collman Advances in macrophage and dendritic cell biology in HIV-1 infection stress key understudied areas in infection, pathogenesis, and analysis of viral reservoirs J. Leukoc. Biol., November 1, 2006; 80(5): 961 - 964. [Abstract] [Full Text] [PDF]
|
|
