T cell induction

Figure 7 Immunopotentiating reconstituted influenza virosomes (IRIV) mediated adjuvance in cytotoxic T-cell induction requires CD4+ T cells. CD8+ and CD14+ cells were cultured in the presence of autologous intact or irradiated CD4+ cells. These cultures were stimulated with influenza matrix (IM)58 66 (1 Pg/mL) alone (A) or supplemented with IRIV (1 50) (B). After seven days of incubation both cocultures were restimulated with irradiated IMss-ee pulsed CD14+ cells and cultured for six further days in the presence of interleukin-2 [see Materials and Methods ]. Six days after restimulation, cultures were stained with HLA-A0201 /IM58-66 PE-specilic tetramers and anti-CD8 fluorescein isothiocyanate monoclonal antibodies. Source. From Ref 6.

Takahashi T, Kuniyasu Y, Toda M, Sakaguchi N, Itoh M, Iwata M et al. Immunologic self-tolerance maintained by CD25-I-CD4-I- naturally anergic and suppressive T cells induction of autoimmune disease by breaking their anergic/suppressive state. Int Immunol 1998 10 1969-1980. 

Neipel F, Albrecht J-C, Fleckenstein B (1997) Cell-homologous genes in the Kaposi s sarcoma-associated rhadinovirus human herpesvirus 8 determinants of its pathogenicity. J Virol 71 4187 192 Perng GC, Jones C, Ciacci-Zanella J, Stone M, Henderson G, Yukht A, Slanina SM, Hofman FM, Ghiasi H, Nesburn AB, Wechsler SL (2000) Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science 287 1500-1503 Raftery MJ, Behrens CK, Muller A, Krammer PH, Walczak H, Schonrich G (1999) Herpes simplex virus type 1 infection of activated cytotoxic T cells Induction of fratricide as a mechanism of viral immune evasion. J Exp Med 190 1103 1114... 

Mills KH (2009) Designer adjuvants for enhancing the efficacy of infectious disease and cancer vaccines based on suppression of regulatory T cell induction. Immunol Lett 122 (2) 108-111... 

The field of DNA vaccination started when eukaryotic expression vectors were injected into the muscle of laboratory animals [2]. The authors observed protein expression for more than 2 months after injection and noted that no special delivery system was required to obtain this expression. Subsequently, it was demonstrated that antibodies can be induced simply by injecting plasmid DNA into the muscle of mice [3]. Subsequent studies found that the injection of expression plasmids also leads to the induction of a cytotoxic T-cell response. After injection, the DNA enters cells of the vaccinated host and the encoded gene becomes expressed. This eventually leads to the induction of a cellular cytotoxic T-cell, T-helper, and/or humoral (antibody) immune response. 

IFN- 3 reduces the induction by inflammatory cytokines of adhesion molecules and of MHC class I and II complex on endothelial cells, a process preceding attachment and transendothelial migration of T-cells. These anti-inflammatory effects of IFN- 3 exemplify antagonistic actions of type I and type IIIFN. There is, indeed, much clinical evidence for the involvement of IFN-y in inflammatory processes - through activation of iNOS and subsequent secretion of NO - leading to the establishment of autoimmune diseases as for instance in rheumatoid arthritis. 

A broad and vigorons T cell response generally accompanies elimination of HBV as well as HCV infection. By contrast, patients with chronic hepatitis B or C tend to have late, transient, or narrow T cell responses. In a long-term follow-up of HBV-infected patients receiving HPC transplants from HBV-immune individuals, 20 of 31 recipients cleared their HBV infection (Hui et al. 2005). In principle, these results encourage the development of adoptive T cell transfer strategies for the treatment of chronic viral hepatitis. However, it is still controversial whether induction of an efficient T cell response is the cause or the consequence of viral clearance. Furthermore, T cell responses do not only contribute to virus control but also to disease pathology (Rehermann and Nascimbeni 2005). 

PAMPs and various tissue factors can prime DCs to produce T-cell-polarizing factors [21], IL-12 is a pro-inflammatory cytokine that induces IFN-y and promotes the development of Thl-cell differentiation [31], Other Thl-polarizing factors are IFN-a and IFN-(3 [32] and cell-surface expressed intracellular adhesion molecule (ICAM)-l [33]. On the other hand, it has been shown that NF-kB inducing kinase (NIK), which is known to regulate B-cell maturation and lymphoid organogenesis, is important for the induction of Thl7 cells [34],... 

Fig. 4. Regulatory T-cell functions suppression of DCs that support the generation of effector T cells suppression of ThI, Th2, and ThI 7 cells suppression of allergen-specific IgE and induction of lgG4, IgA, or both suppression of mast cells, basophils, and eosinophils interaction with resident tissue cells and remodeling, and suppression of effectorT-cell migration to tissues. 

Inhibition of human allergic T-helper type 2 immune responses by induced regulatory T cells requires the combination of interleukin- 10-treated dendritic cells and transforming growth factor-p for their induction. Clin Exp Allergy 2006 36 1546-1555. 

Francis JN, Till SJ, Durham SR Induction of 1L-10+CD4+CD25+ T cells by grass pollen immunotherapy. J Allergy Clin Immunol 2003 111 1255-1261. Jutel M, Akdis M, Budak F, Aebischer-Casaulta C. Wrzyszcz M, Blaser K, Akdis CA lL-10 and TGF-P cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol 2003 33 1205-1214. 

HiBASAMi H, ACHiwA Y, FUJIKAWA T and KOMIYA T (1996) Induction of programmed cell death (apoptosis) in human lymphoid leukemia cells by catechin compounds . Anticancer Res, 16, 1943-46. 

After activation, cytotoxic T cells emerge from lymphoid organs to infiltrate the graft and trigger the immune response. These cells have been shown to induce graft destruction via two mechanisms (1) secretion of the cytotoxic proteins perforin and granzyme B, and (2) induction of cellular apoptosis... 

Basiliximab and daclizumab are considered monoclonal antibodies. Daclizumab is a humanized antibody that is approximately 10% murine and 90% human, whereas basiliximab is a chimeric antibody that is approximately 30% murine and 70% human.9,11 These agents bind with high affinity to the IL-2 receptor, where they act as CD25 receptor antagonists. These receptors are present on almost all activated T cells. Their role in induction therapy involves inhibiting IL-2-mediated activation of lymphocytes, which is an important step for the clonal expansion of T cells. 

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