Cytotoxic CD8+ T cells

Lymphocytes, the effector cells of the acquired immune system, include morphologically indistinguishable T and B cells, the former divided into CD4+ T helper cells and CD8+ cytotoxic T cells. Since the functions of those cell subsets differ so drastically, it became important to develop tools to distinguish them from each other. Efforts to identify cell subsets according to their expression of different surface antigens have been successful, including various Cluster of Determination (CD) markers (Table 23.1). In addition, cross-reactive monoclonal antibodies, and subsequently developed species-specific polyclonal and monoclonal antibodies towards the major histocompatibility complex (MHC) have been used to label cells in circulation and in tissue sections (Table 23.1). 

The MHC complex and antigen can then be detected such as by CD8 cytotoxic T cells and the cells destroyed. However, the fragments of the hapten complex can also be detected by other cells such as APC, and with the collaboration of T-helper cells, B cells would become activated and antibodies produced. These could then bind to the surface antigen as described for a type II reaction. 

Nagata, M., Santamaria, P., Kawamura, T., Utsugi, T. and Yoon, J. W. (1994). Evidence for the role of CD8+ cytotoxic T cells in the destruction of pancreatic beta-cells in nonobese diabetic mice. J. Immunol. 152, 2042-2050. 

An extension of gene therapy, and one that may turn out to be of worldwide importance, is the use of naked DNA as a vaccine to prevent viral diseases. For example, plasmid DNA can be injected into tissues upon entry, the DNA expresses any cloned gene, such as a viral antigen, that is carried by the plasmid. DNA vaccines have the advantage that the viral protein that is expressed in the cells stimulates both humoral and cell-mediated immunity. Fragments of the synthesized viral protein are carried to the cells surface where they stimulate CD8+ cytotoxic T cells and, thereby, cell mediated-immunity (Figure 23-16). 

Ulrich S, Nicolls MR, Taraseviciene L. Increased regulatory and decreased cd8+ cytotoxic T cells in the blood of patients with IPAH. Respiration 2008 75 272-80. 

CD8+ cytotoxic T-cells (CTL) bind to virally infected, tumour or allogenic cells and induce apoptosis in these target cells via a mechanism that is not prevented by inhibitors of protein and RNA synthesis (Duke et al., 1983 Ostergaard and Clark,... 

Takahashi H, Takeshita T, Morein B, Putney S, Germain RN, Berzofsky JA (1990) Induction of CD8+ cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs. Nature 344 873-875... 

Jager E, Ringhofier M, Karbach J, Arand M, Oesch F, Knuth A. Inverse relationship of melanocyte differentiation antigen expression in melanoma tissues and CD8+ cytotoxic-T-cell responses evidence for immunoselection of antigen-loss variants in vivo. Int J Cancer 1996 66 470 76. 

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