CD8α+ dendritic cell trans presentation of IL-15 to naive CD8+ T cells produces antigen-inexperienced T cells in the periphery with memory phenotype and function.
Various populations of memory phenotype CD8(+) T cells have been described over the last 15-20 y, all of which possess elevated effector functions relative to naive phenotype cells. Using a technique for isolating Ag-specific cells from unprimed hosts, we recently identified a new subset of cells, specific for nominal Ag, but phenotypically and functionally similar to memory cells arising as a result of homeostatic proliferation. We show in this study that these virtual memory (VM) cells are independent of previously identified innate memory cells, arising as a result of their response to IL-15 trans presentation by lymphoid tissue-resident CD8α(+) dendritic cells in the periphery. The absence of IL-15, CD8(+) T cell expression of either CD122 or eomesodermin or of CD8a(+) dendritic cells all lead to the loss of VM cells in the host. Our results show that CD8(+) T cell homeostatic expansion is an active process within the nonlymphopenic environment, is mediated by IL-15, and produces Ag-inexperienced memory cells that retain the capacity to respond to nominal Ag with memory-like function. Preferential engagement of these VM T cells into a vaccine response could dramatically enhance the rate by which immune protection develops.
Integrated Department of Immunology, University of Colorado, Denver, CO 80206, USA.
Tomasz
T
Sosinowski
Jason T
JT
White
Eric W
EW
Cross
Catherine
C
Haluszczak
Philippa
P
Marrack
Laurent
L
Gapin
Ross M
RM
Kedl
D000818:Animals; D017951:Antigen Presentation; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D007114:Immunization; D007156:Immunologic Memory / Q000187:drug effects*; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018183:Transplantation Chimera; D014916:Whole-Body Irradiation
D016827:CD8 Antigens; C431698:CD8alpha antigen; D019409:Interleukin-15; D053646:Interleukin-2 Receptor beta Subunit; D010455:Peptides