Mechanisms of enhanced antigen-specific T cell response following vaccination with a novel peptide-based cancer vaccine and systemic interleukin-2 (IL-2).
Systemic interleukin-2 (IL-2) therapy has been shown to enhance the clinical efficacy of peptide-based cancer vaccines. However, the mechanisms involved in this complex response remain poorly defined. IL-2 is known to be a potent T cell growth factor, but recent studies suggest that IL-2 is also involved in the regulation of T cell immune responses by increasing the susceptibility of proliferating T cells to apoptosis. Using an adoptive transfer model, we demonstrate that the administration of systemic IL-2 significantly enhances the primary and memory immune responses following peptide-based vaccination. In order to define the mechanisms of IL-2 therapy on the antigen-specific T cell response, the kinetics of T cell proliferation, apoptosis, and trafficking were explored. Systemic IL-2 therapy did not appear to alter the kinetics of T cell proliferation immediately following vaccination, but did prolong the proliferative response. Furthermore, IL-2 therapy did not significantly influence apoptosis of proliferating T cells. Such therapy did, however, potentiate L-selectin (CD62L) downregulation on activated antigen-specific T cells, and altered their trafficking confirming their potential therapeutic value. Our findings support the use of systemic IL-2 following peptide-based vaccination, and suggest that IL-2 therapy enhances the primary and memory immune responses by prolonging the proliferative response and altering the trafficking of antigen-specific T cells.
Department of Surgery, Section of Surgical Oncology, Medical University of South Carolina, Room 420P, 96 Jonathan Lucas Street, PO Box 250613, Charleston, SC 29425, USA.
Christophe L
CL
Nguyen
Mohamed L
ML
Salem
Mark P
MP
Rubinstein
Marina
M
Demcheva
John N
JN
Vournakis
David J
DJ
Cole
William E
WE
Gillanders
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002455:Cell Division; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013945:Thymoma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D013953:Thymus Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology
D019496:Cancer Vaccines; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor