title: CD1d-dependent expansion of NKT follicular helper cells in vivo and in vitro is a product of cellular proliferation and differentiation.
abstract: NKT follicular helper cells (NKTfh cells) are a recently discovered functional subset of CD1d-restricted NKT cells. Given the potential for NKTfh cells to promote specific antibody responses and germinal center reactions, there is much interest in determining the conditions under which NKTfh cells proliferate and/or differentiate in vivo and in vitro. We confirm that NKTfh cells expressing the canonical semi-invariant Vα14 TCR were CXCR5(+)/ICOS(+)/PD-1(+)/Bcl6(+) and increased in number following administration of the CD1d-binding glycolipid α-galactosylceramide (α-GC) to C57Bl/6 mice. We show that the α-GC-stimulated increase in NKTfh cells was CD1d-dependent since the effect was diminished by reduced CD1d expression. In vivo and in vitro treatment with α-GC, singly or in combination with IL-2, showed that NKTfh cells increased in number to a greater extent than total NKT cells, but proliferation was near-identical in both populations. Acquisition of the NKTfh phenotype from an adoptively transferred PD-1-depleted cell population was also evident, showing that peripheral NKT cells differentiated into NKTfh cells. Therefore, the α-GC-stimulated, CD1d-dependent increase in peripheral NKTfh cells is a result of cellular proliferation and differentiation. These findings advance our understanding of the immune response following immunization with CD1d-binding glycolipids.
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Pragya
authors.initials: P
authors.lastname: Rampuria
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA mark-lang@ouhsc.edu.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Lang
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage; D018858:Germinal Center / Q000276:immunology*; D066298:In Vitro Techniques; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000637:transplantation; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D054380:Receptors, CXCR5 / Q000378:metabolism
chemical_list: D055610:Antigens, CD1d; C490010:Bcl6 protein, mouse; C513179:CXCR5 protein, mouse; D004268:DNA-Binding Proteins; D005699:Galactosylceramides; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D051560:Proto-Oncogene Proteins c-bcl-6; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054380:Receptors, CXCR5; C493154:alpha-galactosylceramide
keywords: CD1d; NKT cells; follicular helper cells