Turning immunological memory into amnesia by depletion of dividing T cells

B Bellier, V Thomas-Vaslin… - Proceedings of the …, 2003 - National Acad Sciences
Proceedings of the National Academy of Sciences, 2003National Acad Sciences
Immunological memory, defined as more efficient immune responses on antigen
reexposure, can last for decades. The current paradigm is that memory is maintained by
antigen-experienced “memory T cells” that can be long-lived quiescent or dividing. The
contribution of T cell division to memory maintenance is poorly known and has important
clinical implications. In this study, we directly addressed the role of dividing T cells in
immunological memory maintenance by evaluating the consequences of their elimination …
Immunological memory, defined as more efficient immune responses on antigen reexposure, can last for decades. The current paradigm is that memory is maintained by antigen-experienced “memory T cells” that can be long-lived quiescent or dividing. The contribution of T cell division to memory maintenance is poorly known and has important clinical implications. In this study, we directly addressed the role of dividing T cells in immunological memory maintenance by evaluating the consequences of their elimination. The specific ablation of dividing T cells was obtained by administration of ganciclovir to immune mice expressing the herpes simplex type 1 thymidine kinase suicide gene in T cells. We show that depletion of dividing T cells for 5 or 2 weeks suffices to abolish in vitro and in vivo memory responses against the male H-Y transplantation alloantigen or against lymphocytic choriomeningitis virus antigens, respectively. Similar results were obtained after the nonspecific elimination of all dividing cells by using hydroxyurea, a cytostatic toxic agent commonly used for cancer chemotherapy. This immune amnesia occurred in otherwise immunocompetent mice and despite the persistence of functional quiescent T cells displaying a “memory” phenotype. Thus, division of antigen-experienced T cells is an absolute requirement for immunological memory maintenance and the current concept of memory T cells is challenged.
National Acad Sciences