Class II-transfected tumor cells directly present endogenous antigen to CD4+ T cells in vitro and are APCs for tumor-encoded antigens in vivo

被引:30
|
作者
Armstrong, TD [1 ]
Clements, VK [1 ]
Ostrand-Rosenberg, S [1 ]
机构
[1] Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA
来源
JOURNAL OF IMMUNOTHERAPY | 1998年 / 21卷 / 03期
关键词
major histocompatibility complex class II; tumor immunity; antigen presentation; CD4(+) T cells;
D O I
10.1097/00002371-199805000-00008
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We have previously demonstrated that class II-transfected tumor cells are very effective immunogens that protect against wild-type primary and metastatic tumor and, if supertransfected with genes encoding co-stimulatory molecules, are immunotherapeutic agents that successfully treat mice with established solid tumor. These results are consistent with our hypothesis that the class II-transfected tumor cells act as antigen-presenting cells (APCs) that directly activate tumor-specific CD4(+) T cells; however, direct data supporting this hypothesis are lacking. In the present study, we test this hypothesis using class II-transfected tumor cells supertransfected with the hen egg lysozyme gene as a surrogate turner antigen. In vitro antigen presentation assays demonstrate that class II-transfected tumor cells present to CD4(+) T cells endogenously encoded tumor antigen, provided they do not co-express the class II-associated invariant chain. In vivo experiments using genetically marked tumor cells and host APCs demonstrate that both class II-transfected tumor cells and host cells are APCs for tumor-encoded antigens, although tumor cells appear to dominate the response. These results support the hypothesis that the immunogenicity and therapeutic value of class II-transfected tumor cells stem from their ability to function as APCs for tumor-encoded antigens and directly activate tumor-specific CD4(+) T lymphocytes.
引用
收藏
页码:218 / 224
页数:7
相关论文
共 50 条
  • [1] MHC class II-transfected tumor cells directly present antigen to tumor-specific CD4+ T lymphocytes
    Armstrong, TD
    Clement, VK
    Ostrand-Rosenberg, S
    [J]. JOURNAL OF IMMUNOLOGY, 1998, 160 (02): : 661 - 666
  • [2] Major histocompatibility complex class II-transfected tumor cells present endogenous antigen and are potent inducers of tumor-specific immunity
    Armstrong, TD
    Clements, VK
    Martin, BK
    Ting, JPY
    OstrandRosenberg, S
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (13) : 6886 - 6891
  • [3] Rejection of MHC class II-transfected tumor cells requires induction of tumor-encoded B7-1 and/or B7-2 costimulatory molecules
    Baskar, S
    Clements, VK
    Glimcher, LH
    Nabavi, N
    OstrandRosenberg, S
    [J]. JOURNAL OF IMMUNOLOGY, 1996, 156 (10): : 3821 - 3827
  • [4] PRESENTATION OF ENDOGENOUS TUMOR-ANTIGENS TO CD4+ T-LYMPHOCYTES BY MURINE MELANOMA-CELLS TRANSFECTED WITH MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II GENES
    CHEN, PW
    ULLRICH, SE
    ANANTHASWAMY, HN
    [J]. JOURNAL OF LEUKOCYTE BIOLOGY, 1994, 56 (04) : 469 - 474
  • [5] γδ T cells present antigen to CD4+ αβ T cells
    Collins, RA
    Werling, D
    Duggan, SE
    Bland, AP
    Parsons, KR
    Howard, CJ
    [J]. JOURNAL OF LEUKOCYTE BIOLOGY, 1998, 63 (06) : 707 - 714
  • [6] The role of MHC class II-restricted tumor antigens and CD4+ T cells in antitumor immunity
    Wang, RF
    [J]. TRENDS IN IMMUNOLOGY, 2001, 22 (05) : 269 - 276
  • [7] Tumor cells present MHC class II-restricted nuclear and mitochondrial antigens and are the predominant antigen presenting cells in vivo
    Qi, L
    Rojas, JM
    Ostrand-Rosenberg, S
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 165 (10): : 5451 - 5461
  • [8] Tumor cells present MHC class II-restricted nuclear and mitochondrial antigens and are predominant antigen presenting cells in vivo
    Qi, L
    Rojas, JM
    Ostrand-Rosenberg, S
    [J]. FASEB JOURNAL, 2001, 15 (05): : A1022 - A1022
  • [9] CD4+ T-cell-Mediated Rejection of MHC Class II-Positive Tumor Cells Is Dependent on Antigen Secretion and Indirect Presentation on Host APCs
    Haabeth, Ole Audun W.
    Fauskanger, Marte
    Manzke, Melanie
    Lundin, Katrin U.
    Corthay, Alexandre
    Bogen, Bjarne
    Tveita, Anders A.
    [J]. CANCER RESEARCH, 2018, 78 (16) : 4573 - 4585
  • [10] Activated CD4+ T Cells Dramatically Enhance Chemotherapeutic Tumor Responses In Vitro and In Vivo
    Radfar, Soroosh
    Wang, Yixiang
    Khong, Hung T.
    [J]. JOURNAL OF IMMUNOLOGY, 2009, 183 (10): : 6800 - 6807