Role of IL-2 secreted by PADRE-specific CD4+ T cells in enhancing E7-specific CD8+ T-cell immune responses.
CD4(+) T helper cells are known to play an integral role in the generation of CD8(+) T-cell immune responses. We have previously shown that co-administration of DNA vaccines containing E6 or E7 protein of human papillomavirus 16 (HPV-16) combined with DNA encoding invariant (Ii) chain in which class II-associated Ii peptide (CLIP) region is replaced with the CD4(+) T helper epitope, PADRE (Pan-DR-epitope) (Ii-PADRE DNA) enhanced HPV antigen-specific CD8(+) T-cell immune responses in vaccinated mice. In the current study, we investigated the enhancement of HPV E7-specific CD8(+) T-cell immune responses by PADRE-specific CD4(+) T cells. We showed that intradermal administration of Ii-PADRE DNA at the same location as E7-expressing DNA is necessary to generate strong E7-specific CD8(+) T-cell immune responses. We also showed that PADRE-specific CD4(+) T cells generated by Ii-PADRE DNA vaccination expressed Th1 cytokine profile. Furthermore, our in vitro study demonstrated that PADRE-specific CD4(+) T cells stimulated with PADRE-loaded dendritic cells secrete IL-2 that leads to the proliferation of E7-specific CD8(+) T cells. Thus, our data suggest that activated PADRE-specific CD4(+) T helper cells may be required at the vicinity of E7-specific CD8(+) T cells where they secrete IL-2, which enhances the E7-specific CD8(+) T-cell immune responses generated by DNA vaccination.
Kim
D
D
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Monie
A
A
He
L
L
Tsai
Y-C
YC
Hung
C-F
CF
Wu
T-C
TC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D052162:Human papillomavirus 16 / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000517:prevention & control; D053918:Papillomavirus Vaccines; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics
D000911:Antibodies, Monoclonal; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16