The longevity of memory CD8 T cell responses after repetitive antigen stimulations.
In experimental models in which the Ag-stimulation history of memory CD8 T cell populations was clearly defined (adoptive transfer of a known number of TCR-transgenic memory CD8 T cells), all facets of the ensuing CD8 T cell responses, including proliferative expansion, duration and extent of contraction, diversification of memory CD8 T cell transcriptomes, and life-long survival, were dependent on the number of prior Ag encounters. However, the extent to which sequential adoptive-transfer models reflect the physiological scenario in which memory CD8 T cells are generated by repetitive Ag challenges of individual hosts (no adoptive transfer involved) is not known. Direct comparison of endogenous memory CD8 T cell responses generated in repetitively infected hosts revealed that recurrent homologous boosting was required to preserve the numbers and increase the phenotypic and functional complexity of the developing memory CD8 T cell pool. Although life-long survival of the memory CD8 T cells was not impacted, phenotype (i.e., upregulation of CD62L) and function (i.e., homeostatic turnover, Ag-stimulated IL-2 production) of repeatedly stimulated memory CD8 T cells were dependent on time after last Ag encounter. Therefore, repetitive Ag challenges of individual hosts can substantially influence the numerical and functional attributes of polyclonal memory CD8 T cells, a notion with important implications for the design of future vaccination strategies aimed at increasing the number of protective memory CD8 T cells.
Department of Pathology, University of Iowa, Iowa City, IA 52242; and.
Deepa
D
Rai
Department of Pathology, University of Iowa, Iowa City, IA 52242; and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242.
Matthew D
MD
Martin
Department of Pathology, University of Iowa, Iowa City, IA 52242; and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242 vladimir-badovinac@uiowa.edu.
Vladimir P
VP
Badovinac
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000502:physiology*; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D013997:Time Factors
D000942:Antigens, Bacterial; D007376:Interleukin-2