title: Class Ia MHC-deficient BALB/c mice generate CD8+ T cell-mediated protective immunity against Listeria monocytogenes infection.
abstract: CD8(+) T cells are required for protective immunity against intracellular pathogens such as Listeria monocytogenes. In this study, we used class Ia MHC-deficient mice, which have a severe reduction in circulating CD8(+) T cells, to determine the protective capacity of class Ib MHC-restricted T cells during L. monocytogenes infection. The K(b-/-)D(b-/-) mutation was backcrossed onto a C.B10 (BALB/c congenic at H-2 locus with C57BL/10) background, because BALB/c mice are more susceptible to Listeria infection than other commonly studied mouse strains such as C57BL/6. C.B10 K(b-/-)D(b-/-) mice immunized with a sublethal dose of L. monocytogenes were fully protected against a subsequent lethal infection. Adoptive transfer of Listeria-immune splenocyte subsets into naive K(b-/-)D(b-/-) mice indicated that CD8(+) T cells were the major component of this protective immune response. A CD8(+) T cell line isolated from the spleen of a Listeria-infected class Ia MHC-deficient mouse was shown to specifically recognize Listeria-infected cells in vitro, as determined by IFN-gamma secretion and cytotoxicity assays. Adoptive transfer of this T cell line alone resulted in significant protection against L. monocytogenes challenge. These results suggest that even a limited number of class Ib MHC-restricted T cells are sufficient to generate the rapid recall response required for protection against secondary infection with L. monocytogenes.
authors.affiliation: Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: D'Orazio
authors.forename: D G
authors.initials: DG
authors.lastname: Halme
authors.forename: H L
authors.initials: HL
authors.lastname: Ploegh
authors.forename: M N
authors.initials: MN
authors.lastname: Starnbach
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002469:Cell Separation; D003433:Crosses, Genetic; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D007110:Immunity, Active / Q000235:genetics; D008089:Listeria monocytogenes / Q000254:growth & development / Q000276:immunology*; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D