(Many of iheseare eKeetor celte-, mosl or all of which diel

Figure 2 T lymphocyte lifespans.

remain unlabeled, indicating that some of these cells may be long-lived and evidence suggests that some memory T cells revert to a naive phenotype. CDS' T cells appear to have a slightly longer lifespan than CD4+ T cells. Based upon the small amount of data available, 78 T cells differ little in lifespan from aß T cells.

Like B cells, the persistence of memory T cells is influenced by continued antigenic stimulation, however, its obligatory role is still controversial. Recent evidence suggests that CD8+ T cells may be less antigen-dependent than CD44 T cells. The study of this question and others relating to lymphocyte lifespan may be facilitated by the use of TCR transgenic mice, as it will then be possible to follow the fate of a cohort of antigen-specific cells in the presence or absence of antigen. However, there are pitfalls to avoid with this methodology. Transfer into empty vessels, such as SCID (severe combined immunodeficiency) or RAGl/RAG2-deficient mice may give rise to exaggerated estimates of lifespan as there is no pressure upon the reconstituting cells from repopulating precursors from primary lymphoid organs. Conversely, transfer into intact mice may give very short estimates, although potentially a stable chitnerism can be achieved that would allow analysis of the subsequent decay in numbers over time. For reasons not entirely clear, but probably due to encounter with environmental or cross-reactive antigens, T cells expand dramatically after transfer into depleted hosts. For this reason it may be necessary to use TCR transgenic mice that have been backcrossed on to a RAG-deficient background to circumvent antigen non-specific effects on cells with endogenous TCR rearrangements.

Effector T cells are generally thought of as terminally differentiated cells with a short lifespan (3— 4 days). However, one theory of memory T cell development proposes that a small proportion of effector cells avoid cell death and become memory cells. It remains to be seen if this is correct or if memory and effector T cells develop along separate pathways of differentiation.

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