Fuc-TVII is required for T helper 1 and T cytotoxic 1 lymphocyte selectin ligand expression and recruitment in inflammation, and together with Fuc-TIV regulates naive T cell trafficking to lymph nodes.
To determine how the alpha(1,3)fucosyltransferases Fuc-TIV and Fuc-TVII, and the selectin ligands they control may contribute to the adaptive immune response, contact hypersensitivity (CHS) was characterized in mice deficient in either or both enzymes. We find a substantial CHS deficiency in Fuc-TVII(-/-) mice, and a complete deficiency in Fuc-TIV(-/-)/Fuc-TVII(-/-) mice. These defects are not accounted for by alterations in the number or function of epidermal Langerhans cells required for cutaneous antigen processing and presentation. By contrast, defective CHS in Fuc-TVII(-/-) mice or Fuc-TIV(-/-)/Fuc-TVII(-/-) mice is attributed in part to prominent, or nearly complete deficiencies, respectively, in the complement of naive T lymphocytes available in lymph nodes for antigen-dependent activation, expansion, differentiation, and dissemination. Fuc-TVII deficiency also deletes expression of E- and P-selectin ligands by Th1 and T cytotoxic 1 (Tc1) lymphocytes, annuls T cell trafficking to inflamed cutaneous sites in vivo, and thereby controls an essential component of the efferent phase of the cutaneous immune response. These observations indicate that collaborative contributions of Fuc-TIV and Fuc-TVII to L-selectin ligand synthesis, and to lymphocyte recruitment, are requisite components of the primary cellular immune response, and assign an essential role to Fuc-TVII in control of E- and P-selectin ligand expression by Th1 and Tc1 lymphocytes.
Smithson
G
G
Department of Pathology, The University of Michigan, Ann Arbor, Michigan 48109, USA.
Rogers
C E
CE
Smith
P L
PL
Scheidegger
E P
EP
Petryniak
B
B
Myers
J T
JT
Kim
D S
DS
Homeister
J W
JW
Lowe
J B
JB
D000818:Animals; D002454:Cell Differentiation; D016764:Cell Polarity; D019040:E-Selectin / Q000378:metabolism; D005434:Flow Cytometry; D005647:Fucosyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology; D007801:Langerhans Cells / Q000166:cytology / Q000502:physiology; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000378:metabolism; D019087:Selectins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*
D019040:E-Selectin; D008024:Ligands; D019007:P-Selectin; D019087:Selectins; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase