Mutation in the Fas pathway impairs CD8+ T cell memory.
Fas death pathway is important for lymphocyte homeostasis, but the role of Fas pathway in T cell memory development is not clear. We show that whereas the expansion and contraction of CD8+ T cell response against Listeria monocytogenes were similar for wild-type (WT) and Fas ligand (FasL) mutant mice, the majority of memory CD8+ T cells in FasL mutant mice displayed an effector memory phenotype in the long-term in comparison with the mainly central memory phenotype displayed by memory CD8+ T cells in WT mice. Memory CD8+ T cells in FasL mutant mice expressed reduced levels of IFN-gamma and displayed poor homeostatic and Ag-induced proliferation. Impairment in CD8+ T cell memory in FasL mutant hosts was not due to defective programming or the expression of mutant FasL on CD8+ T cells, but was caused by perturbed cytokine environment in FasL mutant mice. Although adoptively transferred WT memory CD8+ T cells mediated protection against L. monocytogenes in either the WT or FasL mutant hosts, FasL mutant memory CD8+ T cells failed to mediate protection even in WT hosts. Thus, in individuals with mutation in Fas pathway, impairment in the function of the memory CD8+ T cells may increase their susceptibility to recurrent/latent infections.
Dudani
Renu
R
National Research Council of Canada, Institute for Biological Sciences, Ottawa, Ontario, Canada.
Russell
Marsha
M
van Faassen
Henk
H
Krishnan
Lakshmi
L
Sad
Subash
S
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D053222:Fas Ligand Protein / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D007156:Immunologic Memory / Q000235:genetics*; D016130:Immunophenotyping; D008088:Listeriosis / Q000235:genetics / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009154:Mutation; D010047:Ovalbumin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D012008:Recurrence; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
D053222:Fas Ligand Protein; D019014:fas Receptor; D010047:Ovalbumin