Human NKp44+IL-22+ cells and LTi-like cells constitute a stable RORC+ lineage distinct from conventional natural killer cells.
Lymphoid tissue inducer (LTi) cells are required for lymph node formation during fetal development, and recent evidence implies a role in mucosal immunity in the adult. LTi cells share some phenotypic features of conventional natural killer (NK; cNK) cells; however, little is known to date about the relationship between these two cell types. We show that lineage(-) (Lin(-)) CD127(+)RORC(+) LTi-like cells in human tonsil are precursors to CD56(+)CD127(+)RORC(+)NKp46(+) cells, which together comprise a stable RORC(+) lineage. We find that LTi-like cells and their CD56(+) progeny can be expanded and cloned ex vivo without loss of function and without conversion into cNK cells. Clonal analysis reveals heterogeneity of cytokine production within the CD127(+) LTi-like population. Furthermore, we identify within the tonsil a cNK precursor population that is characterized as Lin(-)CD117(+)CD161(+)CD127(-) cells. Overall, we propose that CD127(+)RORC(+) cells, although they share some characteristics with cNK cells, represent a functionally and developmentally distinct lineage.
Department of Immunology, Genentech, South San Francisco, CA 94080, USA.
Natasha K
NK
Crellin
Sara
S
Trifari
Charles D
CD
Kaplan
Tom
T
Cupedo
Hergen
H
Spits
D000328:Adult; D002454:Cell Differentiation; D019070:Cell Lineage; D006801:Humans; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000276:immunology; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000276:immunology; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000276:immunology / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000276:immunology / Q000378:metabolism; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology; D000097043:Interleukin-22
D053699:Interleukin-7 Receptor alpha Subunit; D007378:Interleukins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D055629:Natural Cytotoxicity Triggering Receptor 2; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D019009:Proto-Oncogene Proteins c-kit; D000097043:Interleukin-22; C527203:KLRB1 protein, human; C112837:NCR2 protein, human; C539900:RORC protein, human