TRAIL Deficiency Delays, but Does Not Prevent, Erosion in the Quality of "Helpless" Memory CD8 T Cells

• Published in: Journal of Immunology 2006-07, Vol.177 (2), p.999-1006
• Main Authors: Badovinac, Vladimir P, Messingham, Kelly A. Nordyke, Griffith, Thomas S, Harty, John T
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis Regulatory Proteins - deficiency; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - physiology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - virology; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Proliferation; Epitopes, T-Lymphocyte - immunology; Homeostasis - genetics; Homeostasis - immunology; Immunologic Memory - genetics; Immunologic Memory - immunology; Immunophenotyping; Lymphocyte Depletion; Lymphocytic Choriomeningitis - immunology; Lymphocytic Choriomeningitis - metabolism; Lymphocytic Choriomeningitis - pathology; Lymphocytic choriomeningitis virus; Lymphocytic choriomeningitis virus - immunology; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; T-Lymphocytes, Helper-Inducer - cytology; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Time Factors; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha - deficiency; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.177.2.999

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.