Memory CD8+ T cells exhibit increased antigen threshold requirements for recall proliferation.
A hallmark of immunological memory is the ability of previously primed T cells to undergo rapid recall responses upon antigen reencounter. Classic work has suggested that memory T cells proliferate in response to lower doses of antigen than naive T cells and with reduced requirements for co-stimulation. In contrast to this premise, we observed that naive but not memory T cells proliferate in vivo in response to limited antigen presentation. To reconcile these observations, we tested the antigen threshold requirement for cell cycle entry in naive and central memory CD8(+) T cells. Although both naive and memory T cells detect low dose antigen, only naive T cells activate cell cycle effectors. Direct comparison of TCR signaling on a single cell basis indicated that central memory T cells do not activate Zap70, induce cMyc expression, or degrade p27 in response to antigen levels that activate these functions in naive T cells. The reduced sensitivity of memory T cells may result from both decreased surface TCR expression and increased expression of protein tyrosine phosphatases as compared with naive T cells. Our data describe a novel aspect of memory T cell antigen threshold sensitivity that may critically regulate recall expansion.
Department of Immunology and 2 the Howard Hughes Medical Institute, University of Washington, Seattle, WA 98109.
Erin R
ER
Mehlhop-Williams
Michael J
MJ
Bevan
D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism
D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin