Biology Reference
In-Depth Information
CD28
ÿ
CD8
T cells. If these cells are simply anergic, as has been suggested
(Lewis et al., 1994), alternative and enhanced costimulatory strategies may be
required to reverse or overcome the unresponsive state. However, if these cells
represent the end stage of replicative senescence, as we propose, gene therapy
techniques such as those that have reversed senescence in other cell types may
be more promising approaches. Moreover, vaccine protocols that target CD8 T
cells may also require consideration of possible strategies to ensure that T-cell
protection is not diminished over time by exhaustion of proliferative potential
of antigen-speci®c CD8 T cells.
CONCLUSION
Telomere studies have highlighted a previously unrecognized aspect of CD8
T-cell biology occurring during HIV disease. The demonstration that the non-
proliferative CD28
ÿ
CD8
T-cell supbpopulation with telomeres in the identical
5±7 kb range, previously associated with replicative senescence reaches levels
of >65% in HIV-infected persons, further underscores the biological relevance
of these observations. In light of the increasing recognition of the importance of
the protective role of CD8 T-cell in HIV disease, it seems clear that research
aimed at retarding CD8 T-cell telomere shortening and delaying replicative
senescence might lead to novel immunotherapeutic strategies that will com-
plement treatments aimed at the virus itself.
Acknowledgments. This work was supported by the National Institutes of
Health (grants AG 10415, AI 35040, AI 28697), amFAR, UC BioSTAR pro-
gram, Geron Corporation, Universitywide AIDS Research Program, and the
UCLA Center on Aging.
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