Depletion of naive T cells of the peripheral lymph nodes abrogates systemic antitumor protection conferred by IL-2 secreting cancer vaccines.
It has been postulated that IL-2 secreting cancer vaccines establish antitumor immunity because the cytokine acting in a paracrine fashion would deliver a helper signal directly to the T cells making contact with the modified tumor cells at the site of vaccination. However, patterns of lymphocyte recirculation cannot be reconciled with the above direct interaction model: only primed memory T cells rather than naive T lymphocytes patrol the periphery, while naive T cells travel to the peripheral lymph nodes, where priming occurs. We have found that in vivo treatment of mice with the antibody MEL-14 directed against L-selectin, which is a molecule expressed at high levels on naive T cells, can completely abrogate protection against a mouse melanoma conferred by an IL-2 secreting vaccine. Since mouse memory CD4 and CD8 T cells are L-selectin-low, only migration of naive T cells is perturbed by the in vivo antibody blockade. Thus, priming of naive T cells in the draining lymph node is a critical step for the successful vaccination by IL-2 secreting cancer vaccines. Such priming is performed most efficiently by professional antigen presenting cells; consequently, these data also imply that allogeneic origin of tumor vaccines may not exclude successful vaccination.
Schweighoffer
T
T
Research Institute for Molecular Pathology, Vienna, Austria.
Schmidt
W
W
Buschle
M
M
Birnstiel
M L
ML
D000818:Animals; D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D019496:Cancer Vaccines / Q000276:immunology*; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D019041:L-Selectin / Q000276:immunology; D037181:Lectins, C-Type; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000517:prevention & control*; D051379:Mice; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014611:Vaccination; D000099192:CD69 Antigens
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019496:Cancer Vaccines; D007376:Interleukin-2; D019041:L-Selectin; D037181:Lectins, C-Type; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens