Roles of CD8 CTLs in Host Defense

In infections by intracellular microbes, the killing activity of CTLs is important for eradication of the reservoir of infection (see Fig. 10-1B). There are two types of situations in which cells cannot destroy microbes that infect them. First, some viruses live and replicate in cells that are incapable of destroying microbes (such as hepatitis viruses in liver cells). Second, even in phagocytes, some microbes escape from vesicles and live in the cytoplasm, where the microbicidal mechanisms of phagocytes are ineffective because these mechanisms are largely restricted to vesicles (to protect the cells from damage). Such infections can be eliminated only by destroying the infected cells, and in adaptive immune responses, CD8+ CTLs are the principal mechanism for killing infected cells. In addition, the caspases that are activated in target cells by granzymes and FasL cleave many substrates and activate enzymes that degrade DNA, but they do not distinguish between host and microbial proteins. Therefore, by activating nucleases in target cells, CTLs can initiate the destruction of microbial DNA as well as the target cell genome, thereby eliminating potentially infectious DNA. The massive expansion of CD8+ T cells that follows infections (see Fig. 9-12, Chapter 9) provides a large pool of CTLs to combat these infections. Defects in the development and activity of CTLs result in increased susceptibility to viral and some bacterial infections and reactivation of latent virus infections (such as infection by the Epstein-Barr virus), which are normally kept in check by virus-specific CTLs.

Destruction of infected cells by CTLs is a cause of tissue injury in some diseases. For instance, in infection by hepatitis B and C viruses, the infected liver cells are killed by the host CTL (and NK cell) response and not by the viruses. These viruses are not cytopathic, but the host senses and reacts against the infectious microbe and is not able to distinguish microbes that are intrinsically harmful or relatively harmless (see Chapter 18).

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