Generation of PLZF+ CD4+ T cells via MHC class II-dependent thymocyte-thymocyte interaction is a physiological process in humans.
Human thymocytes, unlike mouse thymocytes, express major histocompatibility complex (MHC) class II molecules on their surface, especially during the fetal and perinatal stages. Based on this observation, we previously identified a novel developmental pathway for the generation of CD4+ T cells via interactions between MHC class II-expressing thymocytes (thymocyte-thymocyte [T-T] interactions) with a transgenic mouse system. However, the developmental dissection of this T-T interaction in humans has not been possible because of the lack of known cellular molecules specific for T-T CD4+ T cells. We show that promyelocytic leukemia zinc finger protein (PLZF) is a useful marker for the identification of T-T CD4+ T cells. With this analysis, we determined that a substantial number of fetal thymocytes and splenocytes express PLZF and acquire innate characteristics during their development in humans. Although these characteristics are quite similar to invariant NKT (iNKT) cells, they clearly differ from iNKT cells in that they have a diverse T cell receptor repertoire and are restricted by MHC class II molecules. These findings define a novel human CD4+ T cell subset that develops via an MHC class II-dependent T-T interaction.
Lee
You Jeong
YJ
Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Jeon
Yoon Kyung
YK
Kang
Byung Hyun
BH
Chung
Doo Hyun
DH
Park
Chung-Gyu
CG
Shin
Hee Young
HY
Jung
Kyeong Cheon
KC
Park
Seong Hoe
SH
D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication; D005333:Fetus / Q000196:embryology / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000276:immunology*
D000943:Antigens, Differentiation; D000949:Histocompatibility Antigens Class II; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C513267:Zbtb16 protein, mouse; C092037:ZBTB16 protein, human