A sufficient role of MHC class I molecules on hepatocytes in anti-plasmodial activity of CD8+ T cells in vivo
Although CD8+ T cells are shown to mediate the protective immunity against the liver stages of malaria parasites in mice, whether the direct presentation of malaria antigen by major histocompatibility complex (MHC) class I molecules expressed on the liver of infected host is required for anti-plasmo...
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doaj-8d1472f7d4304238abb92485a211aa112020-11-24T23:17:48ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2015-02-01610.3389/fmicb.2015.00069121040A sufficient role of MHC class I molecules on hepatocytes in anti-plasmodial activity of CD8+ T cells in vivoJing eHuang0Tiffany eTsao1Min eZhang2Urvashi eRai3Moriya eTsuji4Xiangming eLi5Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller UniversityAaron Diamond AIDS Research Center, Affiliate of The Rockefeller UniversityNew York University School of MedicineAaron Diamond AIDS Research Center, Affiliate of The Rockefeller UniversityAaron Diamond AIDS Research Center, Affiliate of The Rockefeller UniversityAaron Diamond AIDS Research Center, Affiliate of The Rockefeller UniversityAlthough CD8+ T cells are shown to mediate the protective immunity against the liver stages of malaria parasites in mice, whether the direct presentation of malaria antigen by major histocompatibility complex (MHC) class I molecules expressed on the liver of infected host is required for anti-plasmodial activity of CD8+ T cells is still unknown. Presently, there is only one CD8+ epitope, SYVPSAEQI, derived from the circumsporozoite protein of Plasmodium yoelii (PyCS), that mediates anti-malarial protection and is presented in the context of a Kd molecule. Therefore, to investigate the mode of anti-plasmodial activity of CD8+ T cells, we have previously generated C57BL/6 transgenic (Tg) mice, in which a Kd molecule is expressed only on hepatocyte (Alb-Kd) or dendritic cell (DC) (CD11c-Kd), by using albumin promoter or CD11c promoter, respectively. We have also generated MHC-I-Kd Tg mice, which express the Kd molecule under the MHC class I (MHC-I) promoter, as a positive control. From splenocytes collected from CD11c-Kd Tg mice immunized with a synthetic peptide, SYVPSAEQI, which corresponds to the CD8+ T-cell epitope of PyCS, emulsified in incomplete Freund's adjuvant (IFA), a PyCS-specific CD8+ T-cell line was generated. This PyCS-specific CD8+T-cell line was then adoptively transferred into a cohort of either MHC-Kd Tg or Alb-Kd Tg mice listed above, as well as wild-type C57BL/6 mice. Then both transferred and non-transferred mice were challenged with live malaria parasites. We found that the adoptive transfer of a PyCS-specific CD8+ T-cell line resulted in a significant inhibition of the parasite burden in the liver of Alb-Kd Tg, as well as MHC-I-Kd Tg mice, but not of C57BL/6 mice. These results indicate that the Kd molecule expressed by hepatocytes is sufficient in mediating the anti-plasmodial activity of PyCS-specific CD8+ T cells in vivo.http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00069/fullLiverMalariaMHC class ICD8+ T cellTransgenic mouse |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jing eHuang Tiffany eTsao Min eZhang Urvashi eRai Moriya eTsuji Xiangming eLi |
spellingShingle |
Jing eHuang Tiffany eTsao Min eZhang Urvashi eRai Moriya eTsuji Xiangming eLi A sufficient role of MHC class I molecules on hepatocytes in anti-plasmodial activity of CD8+ T cells in vivo Frontiers in Microbiology Liver Malaria MHC class I CD8+ T cell Transgenic mouse |
author_facet |
Jing eHuang Tiffany eTsao Min eZhang Urvashi eRai Moriya eTsuji Xiangming eLi |
author_sort |
Jing eHuang |
title |
A sufficient role of MHC class I molecules on hepatocytes in anti-plasmodial activity of CD8+ T cells in vivo |
title_short |
A sufficient role of MHC class I molecules on hepatocytes in anti-plasmodial activity of CD8+ T cells in vivo |
title_full |
A sufficient role of MHC class I molecules on hepatocytes in anti-plasmodial activity of CD8+ T cells in vivo |
title_fullStr |
A sufficient role of MHC class I molecules on hepatocytes in anti-plasmodial activity of CD8+ T cells in vivo |
title_full_unstemmed |
A sufficient role of MHC class I molecules on hepatocytes in anti-plasmodial activity of CD8+ T cells in vivo |
title_sort |
sufficient role of mhc class i molecules on hepatocytes in anti-plasmodial activity of cd8+ t cells in vivo |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Microbiology |
issn |
1664-302X |
publishDate |
2015-02-01 |
description |
Although CD8+ T cells are shown to mediate the protective immunity against the liver stages of malaria parasites in mice, whether the direct presentation of malaria antigen by major histocompatibility complex (MHC) class I molecules expressed on the liver of infected host is required for anti-plasmodial activity of CD8+ T cells is still unknown. Presently, there is only one CD8+ epitope, SYVPSAEQI, derived from the circumsporozoite protein of Plasmodium yoelii (PyCS), that mediates anti-malarial protection and is presented in the context of a Kd molecule. Therefore, to investigate the mode of anti-plasmodial activity of CD8+ T cells, we have previously generated C57BL/6 transgenic (Tg) mice, in which a Kd molecule is expressed only on hepatocyte (Alb-Kd) or dendritic cell (DC) (CD11c-Kd), by using albumin promoter or CD11c promoter, respectively. We have also generated MHC-I-Kd Tg mice, which express the Kd molecule under the MHC class I (MHC-I) promoter, as a positive control. From splenocytes collected from CD11c-Kd Tg mice immunized with a synthetic peptide, SYVPSAEQI, which corresponds to the CD8+ T-cell epitope of PyCS, emulsified in incomplete Freund's adjuvant (IFA), a PyCS-specific CD8+ T-cell line was generated. This PyCS-specific CD8+T-cell line was then adoptively transferred into a cohort of either MHC-Kd Tg or Alb-Kd Tg mice listed above, as well as wild-type C57BL/6 mice. Then both transferred and non-transferred mice were challenged with live malaria parasites. We found that the adoptive transfer of a PyCS-specific CD8+ T-cell line resulted in a significant inhibition of the parasite burden in the liver of Alb-Kd Tg, as well as MHC-I-Kd Tg mice, but not of C57BL/6 mice. These results indicate that the Kd molecule expressed by hepatocytes is sufficient in mediating the anti-plasmodial activity of PyCS-specific CD8+ T cells in vivo. |
topic |
Liver Malaria MHC class I CD8+ T cell Transgenic mouse |
url |
http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00069/full |
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