Enhancement of specific T-lymphocyte responses by monocyte-derived dendritic cells pulsed with E2 protein of human papillomavirus 16 and human p16INK4A
Introduction Prophylactic vaccines are already available for prevention of human papillomavirus (HPV) infection. However, we still await development of therapeutic vaccines with high efficiency for stimulating specific T lymphocytes to clear HPV infection. Objective This study investigates the poten...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
PeerJ Inc.
2020-05-01
|
| Series: | PeerJ |
| Subjects: | |
| Online Access: | https://peerj.com/articles/9213.pdf |
| _version_ | 1827610777659375616 |
|---|---|
| author | Nuchsupha Sunthamala Neeranuch Sankla Jureeporn Chuerduangphui Piyawut Swangphon Wanchareeporn Boontun Supakpong Ngaochaiyaphum Weerayut Wongjampa Tipaya Ekalaksananan Chamsai Pientong |
| author_facet | Nuchsupha Sunthamala Neeranuch Sankla Jureeporn Chuerduangphui Piyawut Swangphon Wanchareeporn Boontun Supakpong Ngaochaiyaphum Weerayut Wongjampa Tipaya Ekalaksananan Chamsai Pientong |
| author_sort | Nuchsupha Sunthamala |
| collection | DOAJ |
| description | Introduction Prophylactic vaccines are already available for prevention of human papillomavirus (HPV) infection. However, we still await development of therapeutic vaccines with high efficiency for stimulating specific T lymphocytes to clear HPV infection. Objective This study investigates the potential for subunits of human p16INK4a protein and E2 protein of HPV16 to stimulate dendritic cells and enhance the specific response of T lymphocytes against HPV-infected cells. Methodology Immunogenic epitopes of HPV16 E2 and p16INK4a proteins were predicted through the common HLA class I and II alleles present in the Thai population. Then, monocyte-derived dendritic cells (MDCs) were pulsed with HPV16 E2 and/or p16INK4a protein s and their maturity assessed. MDCs pulsed with either or both of these proteins at optimal concentrations were used for activation of autologous T lymphocytes and IFN-γ production was measured for specific response function. Results HPV16 E2 and p16INK4a proteins contain various immunogenic epitopes which can be presented by antigen-presenting cells via both HLA class I and II molecules. The stimulation of MDCs with either HPV16 E2 or p16INK4a proteins increased percentages and mean fluorescence intensity (MFI) of CD83+ MDCs in a dose-dependent manner. An optimum concentration of 250 ng/mL and 150 ng/mL of HPV16 E2 and p16INK4a proteins, respectively, stimulated MDCs via the MAPK pathway (confirmed by use of MAPK inhibitors). T lymphocytes could be activated by MDCs pulsed with these proteins, leading to high percentages of both CD4+ IFN-γ+ T lymphocytes and CD8+ IFN-γ+ T lymphocytes. The production of IFN-γ was higher in co-cultures containing MDCs pulsed with HPV16 E2 protein than those pulsed with p16INK4a. Interestingly, MDCs pulsed with a combination of HPV16 E2 and p16INK4a significantly increased IFN-γ production of T lymphocytes. The IFN-γ production was inhibited by both HLA class I and II blockade, particularly in co-cultures with MDCs pulsed with a combination of HPV16 E2 and p16INK4a. Conclusions This suggests that MDCs pulsed with both proteins enhances specific response of both CD4+ and CD8+ T lymphocytes. This study might provide a strategy for further in vivo study of stimulation of T lymphocytes for therapy of HPV-associated cancer. |
| first_indexed | 2024-03-09T07:55:43Z |
| format | Article |
| id | doaj.art-7d4a01640731402e82d0737c03344681 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T07:55:43Z |
| publishDate | 2020-05-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj.art-7d4a01640731402e82d0737c033446812023-12-03T01:00:56ZengPeerJ Inc.PeerJ2167-83592020-05-018e921310.7717/peerj.9213Enhancement of specific T-lymphocyte responses by monocyte-derived dendritic cells pulsed with E2 protein of human papillomavirus 16 and human p16INK4ANuchsupha Sunthamala0Neeranuch Sankla1Jureeporn Chuerduangphui2Piyawut Swangphon3Wanchareeporn Boontun4Supakpong Ngaochaiyaphum5Weerayut Wongjampa6Tipaya Ekalaksananan7Chamsai Pientong8Department of Biology, Faculty of Science, Mahasarakham University, Maha Sarakham, ThailandDepartment of Biology, Faculty of Science, Mahasarakham University, Maha Sarakham, ThailandHPV&EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, ThailandHPV&EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, ThailandDepartment of Biology, Faculty of Science, Mahasarakham University, Maha Sarakham, ThailandDepartment of Biology, Faculty of Science, Mahasarakham University, Maha Sarakham, ThailandHPV&EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, ThailandHPV&EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, ThailandHPV&EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, ThailandIntroduction Prophylactic vaccines are already available for prevention of human papillomavirus (HPV) infection. However, we still await development of therapeutic vaccines with high efficiency for stimulating specific T lymphocytes to clear HPV infection. Objective This study investigates the potential for subunits of human p16INK4a protein and E2 protein of HPV16 to stimulate dendritic cells and enhance the specific response of T lymphocytes against HPV-infected cells. Methodology Immunogenic epitopes of HPV16 E2 and p16INK4a proteins were predicted through the common HLA class I and II alleles present in the Thai population. Then, monocyte-derived dendritic cells (MDCs) were pulsed with HPV16 E2 and/or p16INK4a protein s and their maturity assessed. MDCs pulsed with either or both of these proteins at optimal concentrations were used for activation of autologous T lymphocytes and IFN-γ production was measured for specific response function. Results HPV16 E2 and p16INK4a proteins contain various immunogenic epitopes which can be presented by antigen-presenting cells via both HLA class I and II molecules. The stimulation of MDCs with either HPV16 E2 or p16INK4a proteins increased percentages and mean fluorescence intensity (MFI) of CD83+ MDCs in a dose-dependent manner. An optimum concentration of 250 ng/mL and 150 ng/mL of HPV16 E2 and p16INK4a proteins, respectively, stimulated MDCs via the MAPK pathway (confirmed by use of MAPK inhibitors). T lymphocytes could be activated by MDCs pulsed with these proteins, leading to high percentages of both CD4+ IFN-γ+ T lymphocytes and CD8+ IFN-γ+ T lymphocytes. The production of IFN-γ was higher in co-cultures containing MDCs pulsed with HPV16 E2 protein than those pulsed with p16INK4a. Interestingly, MDCs pulsed with a combination of HPV16 E2 and p16INK4a significantly increased IFN-γ production of T lymphocytes. The IFN-γ production was inhibited by both HLA class I and II blockade, particularly in co-cultures with MDCs pulsed with a combination of HPV16 E2 and p16INK4a. Conclusions This suggests that MDCs pulsed with both proteins enhances specific response of both CD4+ and CD8+ T lymphocytes. This study might provide a strategy for further in vivo study of stimulation of T lymphocytes for therapy of HPV-associated cancer.https://peerj.com/articles/9213.pdfHuman papillomavirus (HPV)HPV16 E2p16INK4aDendritic cellsT lymphocytes |
| spellingShingle | Nuchsupha Sunthamala Neeranuch Sankla Jureeporn Chuerduangphui Piyawut Swangphon Wanchareeporn Boontun Supakpong Ngaochaiyaphum Weerayut Wongjampa Tipaya Ekalaksananan Chamsai Pientong Enhancement of specific T-lymphocyte responses by monocyte-derived dendritic cells pulsed with E2 protein of human papillomavirus 16 and human p16INK4A PeerJ Human papillomavirus (HPV) HPV16 E2 p16INK4a Dendritic cells T lymphocytes |
| title | Enhancement of specific T-lymphocyte responses by monocyte-derived dendritic cells pulsed with E2 protein of human papillomavirus 16 and human p16INK4A |
| title_full | Enhancement of specific T-lymphocyte responses by monocyte-derived dendritic cells pulsed with E2 protein of human papillomavirus 16 and human p16INK4A |
| title_fullStr | Enhancement of specific T-lymphocyte responses by monocyte-derived dendritic cells pulsed with E2 protein of human papillomavirus 16 and human p16INK4A |
| title_full_unstemmed | Enhancement of specific T-lymphocyte responses by monocyte-derived dendritic cells pulsed with E2 protein of human papillomavirus 16 and human p16INK4A |
| title_short | Enhancement of specific T-lymphocyte responses by monocyte-derived dendritic cells pulsed with E2 protein of human papillomavirus 16 and human p16INK4A |
| title_sort | enhancement of specific t lymphocyte responses by monocyte derived dendritic cells pulsed with e2 protein of human papillomavirus 16 and human p16ink4a |
| topic | Human papillomavirus (HPV) HPV16 E2 p16INK4a Dendritic cells T lymphocytes |
| url | https://peerj.com/articles/9213.pdf |
| work_keys_str_mv | AT nuchsuphasunthamala enhancementofspecifictlymphocyteresponsesbymonocytederiveddendriticcellspulsedwithe2proteinofhumanpapillomavirus16andhumanp16ink4a AT neeranuchsankla enhancementofspecifictlymphocyteresponsesbymonocytederiveddendriticcellspulsedwithe2proteinofhumanpapillomavirus16andhumanp16ink4a AT jureepornchuerduangphui enhancementofspecifictlymphocyteresponsesbymonocytederiveddendriticcellspulsedwithe2proteinofhumanpapillomavirus16andhumanp16ink4a AT piyawutswangphon enhancementofspecifictlymphocyteresponsesbymonocytederiveddendriticcellspulsedwithe2proteinofhumanpapillomavirus16andhumanp16ink4a AT wanchareepornboontun enhancementofspecifictlymphocyteresponsesbymonocytederiveddendriticcellspulsedwithe2proteinofhumanpapillomavirus16andhumanp16ink4a AT supakpongngaochaiyaphum enhancementofspecifictlymphocyteresponsesbymonocytederiveddendriticcellspulsedwithe2proteinofhumanpapillomavirus16andhumanp16ink4a AT weerayutwongjampa enhancementofspecifictlymphocyteresponsesbymonocytederiveddendriticcellspulsedwithe2proteinofhumanpapillomavirus16andhumanp16ink4a AT tipayaekalaksananan enhancementofspecifictlymphocyteresponsesbymonocytederiveddendriticcellspulsedwithe2proteinofhumanpapillomavirus16andhumanp16ink4a AT chamsaipientong enhancementofspecifictlymphocyteresponsesbymonocytederiveddendriticcellspulsedwithe2proteinofhumanpapillomavirus16andhumanp16ink4a |