TRAIL deficiency delays, but does not prevent, erosion in the quality of "helpless" memory CD8 T cells.
In this study, we investigated the role of TRAIL in Ag-specific CD8 T cell homeostasis after viral infection. TRAIL deficiency does not influence the kinetics of the Ag-specific CD8 T cell responses, and CD8 T cells in TRAIL-deficient mice were able to expand, contract, and generate functional memory cell numbers that were indistinguishable from TRAIL-sufficient wild-type CD8 T cells after acute lymphocytic choriomeningitis virus infection. Interestingly, the ability of "helpless" CD8 T cells to retain their memory phenotypic and functional (i.e., secondary expansion) characteristics was prolonged in TRAIL-deficient mice compared with wild-type CD4-depleted controls. However, TRAIL deficiency only delayed, but did not prevent, the eventual erosion in the quality of helpless memory CD8 T cells, and that correlated with their inability to respond to a second round of Ag-driven proliferation. These data, which suggest that CD4 help consists of both TRAIL-dependent and -independent components, may help to resolve the current controversy between the early programming and maintenance models that were put forward to explain the role of CD4 T cell help in Ag-specific CD8 T cell homeostasis.
Badovinac
Vladimir P
VP
Department of Microbiology, University of Iowa, 51 Newton Road, Iowa City, IA 52242, USA.
Messingham
Kelly A Nordyke
KA
Griffith
Thomas S
TS
Harty
John T
JT
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics* / Q000276:immunology; D016130:Immunophenotyping; D008212:Lymphocyte Depletion; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D018984:Epitopes, T-Lymphocyte; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha