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of several lysosomal enzymes and granules including perforin, granzymes, and
proteoglycans. NK cells lack antigen speci®city in their target recognition and
lysis. Although NK cells can recognize major histocompatibility complexes
(MHC) class I molecules on some antigen-presenting cells (APC), this recog-
nition leads to inhibition of killing. In contrast, CTL recognize self-MHC class
I (CD8
) or class II (CD4
) molecules on APC and their targets. This unique
characteristic of the CTL and their ability recognize self-antigens ensure that
invading intracellular pathogens are seen and contained by the immune system.
CTL are predominantly CD3
CD8
cells, although CD3
CD4
cells have
been shown to have CTL properties, particularly via the Fas/FasL pathway.
Many in vitro studies have shown that CD4
cells can become cytotoxic when
antigens are presented via the MHC class II pathway or in the absence of
CD8
cells. Indeed, CD4
virus-speci®c e¨ectors have been reported in measles,
herpes, and human immunode®ciency virus (HIV ).
The role of CTL in HIV infection is very clear (Rowland-Jones et al.,
1998a). Much data suggest that CD8
T cells are important in the control of
HIV replication, especially early in the disease (Ada, 1996; Autran et al., 1996;
Connick et al., 1996). Indeed, the lack of a CTL response presages a rapidly
declining course of disease. Vigorous CTL responses have been reported in
HIV-infected people with global impairment of immune functions whereas the
absence of vigorous HIV-speci®c CTL in individuals with fairly good immune
functions has also been reported ( Bernard et al., 1998). This has raised ques-
tions as to the clinical relevance of CTL in HIV progression (Walker and Plata,
1990). We now know that HIV possesses the ability to escape CTL killing by
mutation as well as other cellular evasion strategies. We shall discuss our cur-
rent knowledge of the role of CTL in the control of HIV replication in this
chapter.
ANALYSIS OF CTL
T-cell di¨erentiation and selection in the thymus involves several stages
( Fig. 6.1), culminating in the emergence of immature, di¨erentiated, naive
CD3
CD8
and CD3
CD4
cells bearing the ab T-cell receptors. These naive
cells are released into circulation and typically move between blood and the
secondary lymphoid organs, particularly the lymph nodes. Encounters with
antigen-presenting MHC class I or II cells, respectively, followed by costimu-
latory signals such as CD80/86, leads to the activation and development of
a primary immune response as well as further di¨erentiation of these cells
into e¨ector and memory cells (Mehta-Damani et al., 1994). This activation
also requires the presence of IL-2, which is induced in a ``positive feedback''
manner, and, also, a corresponding up-regulation of the IL-2 receptors on the
surfaces of these cells. The e¨ector T cells are short-lived, usually lasting a few
weeks. In contrast, the memory T cells, which di¨er from the naive T cells in
