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

doi:10.1084/jem.194.5.601

Published online 27 August 2001. doi:10.1084/jem.194.5.601

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© The Rockefeller University Press, 0022-1007/2001/9/601/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 5, September 3, 2001 601-614

Original Article

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

Glennda Smithson^a, Clare E. Rogers^b, Peter L. Smith^b, E. Paul Scheidegger^a, Bronislawa Petryniak^b, Jay T. Myers^b, David S. L. Kim^b, Jonathon W. Homeister^a,b, and John B. Lowe^a,b
^a Department of Pathology, The University of Michigan, Ann Arbor, Michigan 48109
^b Howard Hughes Medical Institute, The University of Michigan, Ann Arbor, Michigan 48109

Correspondence to: John B. Lowe, Howard Hughes Medical Institute, Department of Pathology, University of Michigan Medical Center, MSRBI, Rm. 3510, 1150 West Medical Center Dr., Ann Arbor, MI 48109-0650. Tel:734-647-4779 Fax:734-936-1400 E-mail:johnlowe{at}umich.edu.

To determine how the ${alpha}$ (1,3)fucosyltransferases Fuc-TIV and Fuc-TVII,and the selectin ligands they control may contribute to theadaptive immune response, contact hypersensitivity (CHS) wascharacterized in mice deficient in either or both enzymes. Wefind a substantial CHS deficiency in Fuc-TVII^-/- mice, and acomplete deficiency in Fuc-TIV^-/-/Fuc-TVII^-/- mice. These defectsare not accounted for by alterations in the number or functionof epidermal Langerhans cells required for cutaneous antigenprocessing and presentation. By contrast, defective CHS in Fuc-TVII^-/-mice or Fuc-TIV^-/-/Fuc-TVII^-/- mice is attributed in part toprominent, or nearly complete deficiencies, respectively, inthe complement of naive T lymphocytes available in lymph nodesfor antigen-dependent activation, expansion, differentiation,and dissemination. Fuc-TVII deficiency also deletes expressionof E- and P-selectin ligands by Th1 and T cytotoxic 1 (Tc1)lymphocytes, annuls T cell trafficking to inflamed cutaneoussites in vivo, and thereby controls an essential component ofthe efferent phase of the cutaneous immune response. These observationsindicate that collaborative contributions of Fuc-TIV and Fuc-TVIIto 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- andP-selectin ligand expression by Th1 and Tc1 lymphocytes.

Key Words: fucosyltransferase, selectin, T lymphocyte, Th1, Tc1

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