Cytotoxic T lymphocyte CTL

Therapeutic efficacy of adoptively transferred cytotoxic T lymphocytes (CTL) has been demonstrated in clinical trials for cytomegalovirns (CMV)-associated disease (Walter et al. 1995), for EBV-associated lymphoma (Rooney et al. 1995) and nasopharyngeal carcinoma (Comoli et al. 2005) as well as for chronically active EBV infection (Savoldo et al. 2002). 

Vaccination to induce an adaptive immune response is expected for a broad range of infectious diseases and cancers. Traditional vaccines are mainly composed of live attenuated viruses, whole inactivated pathogens, or inactivated bacterial toxins. In general, these approaches have been successful for developing vaccines that can induce an immune response based on antigen-specific antibody and cytotoxic T lymphocyte (CTL) responses, which kill host cells infected with intracellular organisms (Fig. 1) [1,2], One of the most important current issues in vaccinology is the need for new adjuvants (immunostimulants) and delivery systems. Many of the vaccines currently in development are based on purified subunits, recombinant... 

CpG ODNs are also effective as vaccine adjuvants to enhance adaptive TH1 cellular immune responses.104 In mice, CpG ODNs can trigger strong TH1 responses,105 enhancing the number and function of tumor-specific Cytotoxic T lymphocytes (CTLs) and IFN-y secreting T cells.106 This has resulted in therapeutic vaccines in mouse tumor models where no other approach has shown comparable efficacy, even with large (1 cm) established tumors.107 108 Even without a vaccine, CpG ODNs can induce CD8+ T cell-mediated regression of established tumors with durable memory responses.109... 

Cytotoxic T lymphocyte (CTL) Mediated Assay. This assay is similar to the MLR assay and can be performed in parallel or as a Tier II follow-up to the MLR assay. 

CD8 + T cells are driven by MHC class I molecules and do not require professional APC. CD 45 Ro + CD8 + T cells are increased in early infection and are often maintained in symptomatic disease however, dendritic cells are important in stimulating cytotoxic T lymphocyte (CTL) responses in unprimed CD8 + T cell. CD8 cells may also be subdivided based on their cytokine secretion. CD8 CTL clones produce INF-y, IL-6, TNF-a, and ILIO, whereas suppressor cells produce high levels of cytokines associated with Th-2 cells, including IL-4 and low levels of IL-5, IL-6, and IL-10. 

The potential of immunocytokines was elegantly demonstrated in two separate studies using IL-12 for anti-tmnour therapy. IL-12, a potent stimulator of natural killer cells and cytotoxic T-lymphocytes (CTL), activates the immune system to eradicate the cancer cells. IL-12... 

Figure 22.2 Cellular activation by CpG DNA. CpG DNA directly activates dendritic cells (DCs), monocytes and macrophages, to express increased levels of co-stimu-latory molecules, to increase antigen presentation, and to secrete high levels of chemokines and cytokines, such as interleukin 12 (IL-12), interferon-a(IFN-a), and tumor necrosis factor-a (TNF-a), and monocytes and macro-phages have increased antibody-dependent cellular cytotoxicity (ADCC) activity. NK cells are induced to express IFN-7 by these cytokines acting in concert with CpG, and have increased lytic activity. B cells rapidly produce IL-b and IL-10 and express increased levels of costimulatory molecules. B cells rapidly enter the cell cycle and become resistant to some forms of activation-induced cell death. T cells are not directly activated by CpG, but because of the T helper 1 (Thl)-like cytokine environment, and the increased antigen presenting cell (APC) activity, antigen-specific Thl cells and cytotoxic T lymphocytes (CTL) are generated.

IgM PFC to T cell-independent antigen (e.g., TNP-LPS) Cell-mediated immunity Cytotoxic T lymphocyte (CTL) cytolysis... 

The cellular immune response is mediated by T lymphocytes, so called because their maturation from stem cells occurs in the thymus. In cellular immunity it is the intact T lymphocytes themselves that are responsible for the recognition and killing of foreign invaders. These cells are the cytotoxic T lymphocytes (CTL), also called killer T cells. Other T lymphocytes have another role they provide essential help for B lymphocytes to produce antibodies and so are called helper T cells. 

The major problem associated with recombinant vaccines is related to the immune response that is often only humoral (antibody production) and not cellular (e.g. cytotoxic T-lymphocytes, CTL) (Ellis, 1999). Normally, viral vaccines are able to stimulate both types of immune response, thus avoiding the need for revaccination (Ellis, 1996). 

In experimental mouse studies, TCDD exposure results in thymic atrophy and alterations in an array of adaptive immune responses including delayed-type hypersensitivity (DTH), cytotoxic T lymphocyte (CTL) activity, and T-cell-dependent antibody responses. In contrast, TCDD enhances neutrophil recruitment to the site of antigen challenge. Because both cell-mediated and humoral immunity are suppressed by TCDD and related HAHs, it is not surprising that administration of these compounds to mice results in increased susceptibility to challenge with viral, bacterial, or parasitic diseases, as well as syngeneic tumors. 

Bacon, A., Caparros-Wanderley, W., Zadi, B., and Gregoriadis, G. (2002), Induction of a cytotoxic T lymphocyte (CTL) response to plasmid DNA dehvered by Lipodine ,... 

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