In vitro differentiation from naive to mature E-selectin binding CD4 T cells: acquisition of skin-homing properties occurs independently of cutaneous lymphocyte antigen expression.
We previously showed that skin-homing CD4 T cells in peripheral blood can be subdivided into three populations on the basis of the expression pattern of the cutaneous lymphocyte Ag (CLA) and fucosyltransferase VII (FucT-VII): FucT-VII(+)CLA(-), FucT-VII(+)CLA(+), and FucT-VII(-)CLA(+). In view of the known late appearance of CLA during T cell differentiation, T cells programmed to attain skin-homing properties may start to generate E-selectin-binding epitopes at early stages of differentiation before induction of CLA expression. To this end, the in vitro differentiation from naive to CLA(+) memory T cells was followed after activation with anti-CD3 mAb. Here we demonstrate that naive skin-homing CD4 T cell precursors undergo a linear differentiation process from the FucT-VII(+)CLA(-) phenotype to the FucT-VII(+)CLA(+) phenotype and eventually to the FucT-VII(-)CLA(+) phenotype. The appearance of the FucT-VII(+)CLA(-) subset coincided with or could be immediately followed by the generation of E-selectin binding epitopes, and even after E-selectin-binding epitopes were no longer detectable, CLA remained expressed for prolonged periods of time, suggesting that induction of functional E-selectin ligands depends primarily on the expression of FucT-VII, but not CLA. Immunofluorescence and confocal microscopy studies of these T cells confirm that most E-selectin ligands were found independently of CLA expression.
Takahashi
Ryo
R
Division of Flow Cytometry, Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan. ryo@kyorin-u.ac.jp
Mizukawa
Yoshiko
Y
Yamazaki
Yoshimi
Y
Hayakawa
Kazuhito
K
Hayakawa
Jun
J
Kudo
Akihiko
A
Shiohara
Tetsuo
T
D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D019040:E-Selectin / Q000378:metabolism*; D005647:Fucosyltransferases / Q000096:biosynthesis; D006801:Humans; D016130:Immunophenotyping; D007399:Interphase / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D011485:Protein Binding / Q000276:immunology; D012867:Skin / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D019040:E-Selectin; D008024:Ligands; D008562:Membrane Glycoproteins; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase