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- Title
Lack of Functional Selectin Ligand Interactions Compromises Long Term Tumor Protection by CD8<sup>+</sup> T Cells.
- Authors
Stark, Felicity C.; Gurnani, Komal; Sad, Subash; Krishnan, Lakshmi
- Abstract
Central memory CD8+ T cells expressing the adhesion molecule CD62L (L-selectin) are potent mediators of anti-cancer immunity due to their ability to proliferate extensively upon antigen re-stimulation. The interaction of selectin with its ligands mediates leukocyte rolling along high endothelial venules. Mice deficient in α(1,3) Fucosyltransferase IV and VII (FtDKO) lack functional L, P and E selectin ligands. Thus, we addressed whether the lack of selectin ligand interactions alters tumor protection by CD8+ T cells in FtDKO mice. Listeria monocytogenes-OVA (LM-OVA) infection evoked potent OVAspecific CD8+ T cells that proliferated and contracted at similar kinetics and phenotype in FtDKO and wild-type mice. Additionally, OVA-specific CD8+ T cells in both mouse strains exhibited similar phenotypic differentiation, in vivo cytolytic activity and IFN-γ expression. However, FtDKO mice succumbed to B16-OVA tumors significantly earlier than wild-type mice. In contrast, FtDKO mice evoked strong recall memory CD8+ T cell responses and protection to systemic LM-OVA rechallenge. The diminished tumor protection in FtDKO mice was not related to defective antigen presentation by dendritic cells or reduced proliferation of antigen-specific CD8+ T cells. However, WT or FtDKO OVA-specific CD8+ T cells showed significantly reduced ability to traffic to lymph nodes upon adoptive transfer into naïve FtDKO recipients. Furthermore, FtDKO OVA-specific CD8+ T cells displayed poor ability to infiltrate tumors growing in WT mice. These results reveal that selectin ligand expression on host endothelium as well CD8+ T cells may be important for their efficient and continued extravasation into peripheral tumors.
- Publication
PLoS ONE, 2012, Vol 7, Issue 2, p1
- ISSN
1932-6203
- Publication type
Academic Journal
- DOI
10.1371/journal.pone.0032211