Naïve T cells re-distribute to the lungs of selectin ligand deficient mice.
BACKGROUND
Selectin mediated tethering represents one of the earliest steps in T cell extravasation into lymph nodes via high endothelial venules and is dependent on the biosynthesis of sialyl Lewis X (sLe(x)) ligands by several glycosyltransferases, including two fucosyltransferases, fucosyltransferase-IV and -VII. Selectin mediated binding also plays a key role in T cell entry to inflamed organs.


RESULTS
To understand how loss of selectin ligands (sLe(x)) influences T cell migration to the lung, we examined fucosyltransferase-IV and -VII double knockout (FtDKO) mice. We discovered that FtDKO mice showed significant increases (approximately 5-fold) in numbers of naïve T cells in non-inflamed lung parenchyma with no evidence of induced bronchus-associated lymphoid tissue. In contrast, activated T cells were reduced in inflamed lungs of FtDKO mice following viral infection, consistent with the established role of selectin mediated T cell extravasation into inflamed lung. Adoptive transfer of T cells into FtDKO mice revealed impaired T cell entry to lymph nodes, but selective accumulation in non-lymphoid organs. Moreover, inhibition of T cell entry to the lymph nodes by blockade of L-selectin, or treatment of T cells with pertussis toxin to inhibit chemokine dependent G-coupled receptor signaling, also resulted in increased T cells in non-lymphoid organs. Conversely, inhibition of T cell egress from lymph nodes using FTY720 agonism of S1P1 impaired T cell migration into non-lymphoid organs.


CONCLUSIONS
Taken together, our results suggest that impaired T cell entry into lymph nodes via high endothelial venules due to genetic deficiency of selectin ligands results in the selective re-distribution and accumulation of T cells in non-lymphoid organs, and correlates with their increased frequency in the blood. Re-distribution of T cells into organs could potentially play a role in the initiation of T cell mediated organ diseases.
Harp
John R
JR
Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA.
Onami
Thandi M
TM
D000818:Animals; D000068876:Fingolimod Hydrochloride; D007156:Immunologic Memory; D008024:Ligands; D008168:Lung / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011409:Propylene Glycols / Q000494:pharmacology; D019087:Selectins / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology
D008024:Ligands; D011409:Propylene Glycols; D019087:Selectins; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine