Levitsky H I, Lazenby A, Hayashi R J, Pardoll D M
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Exp Med. 1994 Apr 1;179(4):1215-24. doi: 10.1084/jem.179.4.1215.
Downregulation of major histocompatibility complex (MHC) class I expression is an important mechanism by which tumors evade classical T cell-dependent immune responses. Therefore, a system was designed to evaluate parameters for active immunization against MHC class I- tumors. Mice were capable of rejecting a MHC class I- tumor challenge after immunization with an irradiated granulocyte/macrophage colony-stimulating factor (GM-CSF) transduced MHC class I- tumor vaccine. This response was critically dependent on CD4+ T cells and natural killer (NK) cells, but minimally on CD8+ T cells. A strong protective response against MHC class I+ variants of the tumor could be elicited when mice were immunized with irradiated MHC class I+ GM-CSF-secreting tumor cells. This response required CD4+ and CD8+ T cells, and in addition, elimination of NK cells resulted in outgrowth of tumors that had lost expression of at least one MHC class I gene. Finally, class I MHC expression on the vaccinating cells inhibited the response generated against a MHC class I- tumor challenge. These results demonstrate that the host is capable of being immunized against a tumor that has lost MHC class I expression and reveal conditions under which distinct effector cells play a role in the systemic antitumor immune response.
主要组织相容性复合体（MHC）I类分子表达下调是肿瘤逃避经典的T细胞依赖性免疫反应的重要机制。因此，设计了一个系统来评估针对MHC I类缺陷肿瘤进行主动免疫的参数。在用经辐射的粒细胞/巨噬细胞集落刺激因子（GM-CSF）转导的MHC I类缺陷肿瘤疫苗免疫后，小鼠能够排斥MHC I类缺陷肿瘤攻击。这种反应严重依赖于CD4 + T细胞和自然杀伤（NK）细胞，但对CD8 + T细胞的依赖极小。当用经辐射的分泌GM-CSF的MHC I类阳性肿瘤细胞免疫小鼠时，可引发针对肿瘤的MHC I类阳性变体的强烈保护性反应。这种反应需要CD4 +和CD8 + T细胞，此外，消除NK细胞会导致至少一个MHC I类基因表达缺失的肿瘤生长。最后，接种细胞上的I类MHC表达抑制了针对MHC I类缺陷肿瘤攻击产生的反应。这些结果表明，宿主能够针对已失去MHC I类表达的肿瘤进行免疫，并揭示了不同效应细胞在全身抗肿瘤免疫反应中发挥作用的条件。
