title: Nonconventional CD8+ T cell responses to Listeria infection in mice lacking MHC class Ia and H2-M3.
abstract: CD8(+) T cells restricted to MHC class Ib molecules other than H2-M3 have been shown to recognize bacterial Ags. However, the contribution of these T cells to immune responses against bacterial infection is not well defined. To investigate the immune potential of MHC class Ib-restricted CD8(+) T cells, we have generated mice that lack both MHC class Ia and H2-M3 molecules (K(b-/-)D (b-/-)M3(-/-)). The CD8(+) T cells present in K(b-/-)D (b-/-)M3(-/-) mice display an activated surface phenotype and are able to secrete IFN-γ rapidly upon anti-CD3 and anti-CD28 stimulation. Although the CD8(+) T cell population is reduced in K(b-/-)D (b-/-)M3(-/-) mice compared with that in K(b-/-)D (b-/-) mice, this population retains the capacity to expand significantly in response to primary infection with the bacteria Listeria monocytogenes. However, K(b-/-)D (b-/-)M3(-/-) CD8(+) T cells do not expand upon secondary infection, similar to what has been observed for H2-M3-restricted T cells. CD8(+) T cells isolated from Listeria-infected K(b-/-)D (b-/-)M3(-/-) mice exhibit cytotoxicity and secrete proinflammatory cytokines in response to Listeria-infected APCs. These T cells are protective against primary Listeria infection, as Listeria-infected K(b-/-)D (b-/-)M3(-/-) mice exhibit reduced bacterial burden compared with that of infected β(2)-microglobulin-deficient mice that lack MHC class Ib-restricted CD8(+) T cells altogether. In addition, adoptive transfer of Listeria-experienced K(b-/-)D (b-/-)M3(-/-) splenocytes protects recipient mice against subsequent Listeria infection in a CD8(+) T cell-dependent manner. These data demonstrate that other MHC class Ib-restricted CD8(+) T cells, in addition to H2-M3-restricted T cells, contribute to antilisterial immunity and may contribute to immune responses against other intracellular bacteria.
authors.affiliation: Department of Microbiology and Immunology, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Hoonsik
authors.initials: H
authors.lastname: Cho
authors.forename: Hak-Jong
authors.initials: HJ
authors.lastname: Choi
authors.forename: Honglin
authors.initials: H
authors.lastname: Xu
authors.forename: Kyrie
authors.initials: K
authors.lastname: Felio
authors.forename: Chyung-Ru
authors.initials: CR
authors.lastname: Wang
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006183:H-2 Antigens / Q000235:genetics*; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D001613:beta 2-Microglobulin / Q000172:deficiency* / Q000235:genetics
chemical_list: D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; C078177:H2-M3 antigen; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin