Cytotoxic T-cell response

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. 

Wanschitz, J., Maier, H., Lassmann, H., Budka, H. and Berger, T. Distinct time pattern of complement activation and cytotoxic T cell response in Guillain-Barre syndrome. Brain 126 2034-2042, 2003. 

Storni T, Ruedl C, Schwarz K, Schwendener RA, Renner WA, Bachmann ME. Nonmethylated CG motifs packaged into virus-like particles induce protective cytotoxic T cell responses in the absence of systemic side effects. J Immunol 2004 172(3) 1777-1785. 

Rowland-Jones, S. L., T. Dong, K. R. Fowke, J. Kimani, P. Krausa, H. Newell, T. Blanchard, K. Ariyoshi, J. Oyugi, E. Ngugi, J. Bwayo, K. S. MacDonald, A. J. McMichael, and F. A. Plummer. 1998. Cytotoxic T Cell Responses to Multiple Conserved HIV Epitopes in HIV-Resistant Prostitutes in Nairobi. Journal of Clinical Investigation 102 1758-1765. 

The major immunobiological effect of IL-10 is the regulation of the TH1/TH2 balance. TF cells are involved in cytotoxic T-cell responses whereas TH2 cells regulate B-cell activity and function. IL-10 is a promoter of TH2 response by inhibiting IFN-y production from THi cells. This effect is mediated via the suppression of IL-12 synthesis in accessory cells. IL-10 is involved in assisting against intestinal parasitic infection, local mucosal infection by costimulating the proliferation and differentiation of B cells. Its indirect effects also include the neutralization of bacterial toxins. 

Fomsgaard, A., Nielsen, H.V., Kirkby, N., Bryder, K., Corbet, S., Nielsen, C., Hinkula, J. and Buus, S. (1999) Induction of cytotoxic T-cell responses by gene gun DNA vaccination with minigenes encoding influenza A virus HA and NP CTL-epitopes. Vaccine, 18, 681-691. 

Lipford, G.B., Bauer, M., Blank, C., Reiter, R., Wagner, H. and Heeg, K. (1997) CpG-containing synthetic oligonucleotides promote B and cytotoxic T cell responses to protein antigen a new class of vaccine adjuvants. Eur. J. Immunol., 27, 2340-2344. 

Jackson, D.C., Lau, Y.F., Le, T., et al. (2004) A totally synthetic vaccine of generic structure that targets Toll-like receptor 2 on dendritic cells and promotes antibody or cytotoxic T cell responses. Proc. Natl. Acad. Sci. USA 101(43), 15440-15445. 

Hsu, S.C., Chargelegue, D., Obeid, O.E., and Steward, M.W. (1999) Synergistic effect of immunization with a peptide cocktail inducing antibody, helper and cytotoxic T-cell responses on protection against respiratory syncytial virus. J. Gen. Virol. 80, 1401-1405. 

As described above, peptide epitopes bound to MHC class I or II molecules are able to stimulate CD8+ and CD4+ T cells, respectively. Both CD4+ T-helper cells and CD8+ CTLs are critical to protective immunity and to vaccine efficacy. CD4+ T-helper cells play an important role in the development of memory B-cell (antibody) and memory CTL (cytotoxic T-cell) responses. CD4+ T-helper cells are also active against pathogens on their own. Therefore, CD4+ T-helper cells have been called the conductors of the immune system orchestra (14). CD8+ CTLs are able to directly kill infected target cells and thus are critical in the containment of... 

Richards, R. L., Rao, M., Wassef, N.M., Glenn, G.M., Rothwell, S.W., Alving, C.R. Liposomes containing Lipid A serve as an adjuvant for induction of antibody and cytotoxic T-cell responses against RTS,S malaria antigen. Infect Immun 66 (1998) 2859-2865. 

Koenig S, Woods RM, Brewali YA, Newell AJ, Jones GM, Boone E, Adelsberger JW, Baseler MW, Robinson SM, Jacobson S (1993) Char acteiizadon of MHC class I restiicted cytotoxic T cell responses to tax in HTLV-1 infected patients witli neru ologic disease. J Immunol 151 3874—3883. 

Cytotoxic T cell response and IFN- y production after subcutaneous immunization with NS1851 peptide... 

A needle-free powder injector (Powderject) was used to intradermally deliver DNA vaccines in mice. Nanogram quantities of DNA encoding the nucleoprotein gene of influenza A virus coated to gold particles elicited a strong and a nucleoprotein-specific cytotoxic T cell response in the animals, indicating effectiveness of immunization with the DNA vaccine. 

Martin R, Utz U, Coligan JE, Richert J, Flerlage M, Robinson E, Stone R, Biddison WE, McFarlin DE, McFarland HF (1992) Diversity in fine specificity and T cell receptor usage of the human CD4 + cytotoxic T cell response specific for the immunodominant myelin basic protein peptide 87-106, J Immunol 148 1359-1366. 

A select group of studies has helped to shed light on the possible physiological mechanisms by which thymic factors control the expression of functional aspects of immunity. Probably the most consistent effect of thymic factors is their ability to induce suppressor T cell activity in various animal models. For example, TF5 has been shown to induce suppressor cell activity in spleen cells of nude mice for both antibody and cytotoxic T cell responses (Marshall et al., 1981 Ahmed et ah, 1978, 1979). Similar effects have been observed with several purified thymic peptides including Ta (Ahmed, 1978, 1979) and thymulin (summarized in Bach, 1983). Other thymic peptides, such as Taj, appear to be more associated with the generation of functional helper T cells. Similar helper inductive effects have also been observed with thymulin in both normal thymocytes and nude mouse spleen cells, which may result from its ability to enhance the production of T cell growth factor (interleukin-2, IL-2) (Palacios et ah, 1982 Palacios 1983). 

M.L Hedley, J. Curley and R. Urban, Microspheres containing plasmid-encoded antigens elicit cytotoxic T-cell responses. Nature Med. 1996, 4, 365-368. 

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