T-cell priming

Grewel, I.S., Xu, J. and Flavell, R.A. (1995) Impairment of antigen-specific T cell priming in mice lacking CD40 ligand. Nature 378, 617-620. 

Sallusto, F., Lanzavecchia, A and Mackay, C.R. (1998) Chemokine and chemokine receptors in T-cell priming and Thl/Th2-mediated responses. Immunology Today 12, 569-574. 

Gorbachev, A.V. and Fairchild, R.L., Induction and regulation of T-cell priming for contact hypersensitivity. Crit. Rev. Immunol., 21, 451, 2001. 

Layland LE. Rad R. Wagner H. da Costa CU Immunopathology in schistosomiasis is controlled by antigen-specific regulatory T cells primed in the presence of TLR2. Eur J Immunol 2007 37 2174-2184. 

Andrographolide, thus, has different mechanisms of anti-inflammatory activity. It can inhibit the activation of NF-kB, suppress inducible nitric oxide synthase (iNOS) expression, inhibit COX-2 expression in human fibroblast cells and also prevent oxygen radical production by human. The compound is also able to modulate T-cell activation both in vitro as well as in vivo, it is evident that it could prevent initial T-cell priming by interfering with DC maturation and antigen presentation capacity. Therefore, andrographolide may have utility as a therapeutic agent for the treatment of autoimmune diseases, such as multiple sclerosis. " ... 

Segura, E., Nicco, C., Lombard, B., Veron, P., Raposo, G., Batteux, F., Amigorena, S. andThery, C. (2005) ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T cell priming. Blood... 

Cross, A. H., Cannella, B., Brosnan, C. F., and Raine, C. S., Hypothesis antigen-specific T cells prime central nervous system endothelium for recruitment of nonspecific inflammatory cells to effect autoimmune demyelination, J. Neuroimmunol, 33, 237, 1991. 

Mempel TR, Henrickson SE, von Andrian UH (2004) T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427 154-159... 

Holt PG Primary allergic sensitisation to environmental antigens Perinatal T-cell priming as a determinant of responder phenotype in adulthood. J Exp Med 1996 183 1297-1301. 

According to this theory, viral and bacterial infections might prevent the induction of allergen specific Th2 cells because they establish Thl-biased immunity. Viral (except some respiratory viruses) and bacterial infections that induce strong Thl responses tend to inhibit the development of bystander allergen-specific Th2 cells (Herz et al. 2000) through the production of IFN-y, lL-12 and lL-18 at the site of naive T-cell priming. 

As described, IL-2 binds rapidly to its cellular receptor, which may then be shed from the cell surface into the tissue fluid and from there to the peripheral blood. IL-2 itself has a much shorter half-life than that of the shed receptor. The presence of the soluble receptor is thus a better measure of IL-2 activity than levels of the cytokine itself (R30). IL-2 activity has been a prime target for research into better markers of rejection as it is a key component in T-cell priming for allograft rejection and could be expected to change at a very early stage. 

Optimization of the Antigen Processing and T-cell Priming. When the antigen encoded by the nucleic acid is to be recognized by T lymphocytes, its derived peptide epitopes must be efficaciously presented by MHC class I or class II molecules. Although any cytosolic, membrane or secreted protein can be used to produce MHC I and MHC II associated epitopes, several methods to enhance this presentation were described. 

Kalinski P, Hilkens CMU, Wierenga EA, Kapsenbeig ML T-cell priming by type-1 and type-2 polarized dendritic cells The concept of a third signal. Immunol Today 1999 20 561-567. 

Fig. 1 Tumour immunosurveillance and the role of the main immnne cell types. The immune response against cancer may be initiated by cells of the innate immune system, by external damage to the tumour cells and via other mechanisms. Tumour antigens, taken up by dendritic cells (DC), are carried into secondary lymphoid organs where T cell priming occurs. CD4 + T cells provide help for B cell and CDS + T cell responses. CDS + tumour-antigen-specific T cells become activated and migrate to the periphery where they recognise and destroy malignant cells...

However in our experience inhibition of NOS or iNOS during immunizations could abrogate the effects and underscore the importance of certain levels of NO for T-cell priming. 

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