Content area
Full Text
REVIEW.com/natureimmunologyT cells and viral persistence: lessons from
diverse infectionshttp://www.nature2005 Nature Publishing Group Paul Klenerman1 & Ann Hill2Persistent virus infections create specific problems for their hosts. Although the dynamics of immune responses
after acute infection are well studied and very consistent, especially in mouse models, the patterns of responses
noted during persistent infection are more complex and differ depending on the infection. In particular, CD8+ T cell
responses differ widely in quantity and quality. In this review we examine these diverse responses and ask how they
may arise; in particular, we discuss the function of antigen re-encounter and the CD4+ T cell responses to and the
escape strategies of specific viruses. We focus on studies of four main human pathogens, cytomegalovirus, Epstein-
Barr virus, human immunodeficiency virus and hepatitis C virus, and their animal models.A range of host responses combine to control viral infection during the
acute phase, and the initiation of innate, humoral and cellular immune
responses are well described in a range of animal models. However,
if this fails to eliminate the pathogen, host and virus must establish
some form of long-term relationship in which the immunological rules
may be somewhat different from those of a brief encounter. The early
interactions, although not the focus of this review, nevertheless have a
considerable effect on the long-term outcome, such as the progression
of human immunodeficiency virus (HIV) infection.Much work has focused on the analysis of cellular immune responses
during persistent virus infection. This is partly because of the explosion
of new quantitative and qualitative information that has been obtained
since the development of new tools for the ex vivo analysis of T cell
responses. Studies using major histocompatibility complex (MHC)
class Ipeptide tetramers have shown, for example, the diversity that
can be found in CD8+ T cell responses to distinct viruses1. However the
factors shaping such responses and their involvement in determining
the clinical outcome of infection have yet to be defined.In this review we aim both to describe the diversity of T cell responses
noted during infection with various persistent viruses and to discuss
the different models that may explain how they arise. We focus particularly on CD8+ T cells because of their recognized involvement in
the containment of specific virus infections. However, in...