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Stability of Naive and Memory Phenotypes on Resting CD4 T Cells In Vivo¹

Section of Immunobiology, Yale University School of Medicine, and Howard Hughes Medical Institute, New Haven, CT 06511

The reliable identification of naive and memory CD4 T cells is critical to understanding the cellular basis of immunological memory. However, it has long been a controversial issue whether naive and memory phenotypes are stable among resting CD4 T cells in the absence of overt stimulation or whether the proposed memory phenotype is a transient, reversible one that represents recently activated cells. In this study, adoptively transferred, purified populations of naive or memory phenotype CD4 T cells are monitored over time to assess the stability of phenotypes and the functional capabilities of transferred cells. Studying both TCR transgenic and nontransgenic CD4 T cell populations allows one to control for the capacity to respond to environmental Ags in vivo. Several findings are reported. The first is that in the absence of Ag, both naive and memory phenotypes remain unchanged over time. Second, when changes are seen in populations of transferred naive phenotype CD4 T cells, they take place only when there is a potential for antigenic challenge, suggesting that it is an Ag-driven event. Furthermore, when a change from naive to memory phenotype is observed, these transferred donor cells also function as memory cells. Third, the ability of memory CD4 T cells to retain the memory phenotype is independent of specific Ag.

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