title: MHC class II-restricted interaction between thymocytes plays an essential role in the production of innate CD8+ T cells.
abstract: We have recently shown that MHC class II-dependent thymocyte-thymocyte (T-T) interaction successfully generates CD4(+) T cells (T-T CD4(+) T cells), and that T-T CD4(+) T cells expressing promyelocytic leukemia zinc finger protein (PLZF) show an innate property both in mice and humans. In this article, we report that the thymic T-T interaction is essential for the conversion of CD8(+) T cells into innate phenotype in the physiological condition. CD8(+) T cells developed in the presence of PLZF(+) CD4(+) T cells showed marked upregulation of eomesodermin (Eomes), activation/memory phenotype, and rapid production of IFN-γ on ex vivo stimulation. Their development was highly dependent on the PLZF expression in T-T CD4(+) T cells and the IL-4 secreted by PLZF(+) T-T CD4(+) T cells. The same events may take place in humans, as a substantial number of Eomes expressing innate CD8(+) T cells were found in human fetal thymi and spleens. It suggests that PLZF(+) T-T CD4(+) T cells in combination with Eomes(+) CD8(+) T cells might actively participate in the innate immune response against various pathogens, particularly in human perinatal period.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, 110-799 Seoul, Korea.
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Min
authors.forename: You Jeong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Kim
authors.forename: Byung Hyun
authors.initials: BH
authors.lastname: Kang
authors.forename: Kyeong Cheon
authors.initials: KC
authors.lastname: Jung
authors.forename: Cheong-Hee
authors.initials: CH
authors.lastname: Chang
authors.forename: Seong Hoe
authors.initials: SH
authors.lastname: Park
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000276:immunology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D010641:Phenotype; D016133:Polymerase Chain Reaction; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D020825:T-Box Domain Proteins / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology / Q000276:immunology / Q000378:metabolism
chemical_list: C491199:EOMES protein, human; D000949:Histocompatibility Antigens Class II; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D020825:T-Box Domain Proteins; C092037:ZBTB16 protein, human; D015847:Interleukin-4; D007371:Interferon-gamma