Wells James W, Cowled Chris J, Darling David, Guinn Barbara-Ann, Farzaneh Farzin, Noble Alistair, Galea-Lauri Joanna
Department of Haematological and Molecular Medicine, King's College London, The Rayne Institute, London, SE5 9NU, UK.
Cancer Immunol Immunother. 2007 Dec;56(12):1861-73. doi: 10.1007/s00262-007-0328-x. Epub 2007 May 9.
Alloreactive T-cell responses are known to result in the production of large amounts of proinflammatory cytokines capable of activating and maturing dendritic cells (DC). However, it is unclear whether these allogeneic responses could also act as an adjuvant for concurrent antigen-specific responses.
To examine effects of simultaneous alloreactive and antigen-specific T-cell responses induced by semi-allogeneic DC.
Semi-allogeneic DC were generated from the F(1) progeny of inbred strains of mice (C57BL/6 and C3H, or C57BL/6 and DBA). We directly primed antigen-specific CD8(+) and CD4(+) T-cells from OT-I and OT-II mice, respectively, in the absence of allogeneic responses, in vitro, and in the presence or absence of alloreactivity in vivo.
In vitro, semi-allogeneic DC cross-presented ovalbumin (OVA) to naïve CD8(+) OT-I transgenic T-cells, primed naïve CD4(+) OT-II transgenic T-cells and could stimulate strong alloreactive T-cell proliferation in a primary mixed lymphocyte reaction (MLR). In vivo, semi-allogeneic DC migrated efficiently to regional lymph nodes but did not survive there as long as autologous DC. In addition, they were not able to induce cytotoxic T-lymphocyte (CTL) activity to a target peptide, and only weakly stimulated adoptively transferred OT-II cells. The CD4(+) response was unchanged in allo-tolerized mice, indicating that alloreactive T-cell responses could not provide help for concurrently activated antigen-specific responses. In an EL4 tumour-treatment model, vaccination with semi-allogeneic DC/EL4 fusion hybrids, but not allogeneic DC/EL4 hybrids, significantly increased mouse survival.
Expression of self-Major histocompatibility complex (MHC) by semi-allogeneic DC can cause the induction of antigen-specific immunity, however, concurrently activated allogeneic bystander responses do not provide helper or adjuvant effects.
已知同种异体反应性T细胞应答会导致产生大量能够激活和成熟树突状细胞（DC）的促炎细胞因子。然而，尚不清楚这些同种异体反应是否也能作为同时发生的抗原特异性应答的佐剂。
研究半同种异体DC诱导的同种异体反应性和抗原特异性T细胞应答同时发生的效应。
半同种异体DC由近交系小鼠（C57BL/6和C3H，或C57BL/6和DBA）的F1子代产生。我们分别在体外无同种异体反应的情况下，以及在体内有或无同种异体反应的情况下，直接启动来自OT-I和OT-II小鼠的抗原特异性CD8(+)和CD4(+) T细胞。
在体外，半同种异体DC将卵清蛋白（OVA）交叉呈递给未致敏的CD8(+) OT-I转基因T细胞，启动未致敏的CD4(+) OT-II转基因T细胞，并能在初次混合淋巴细胞反应（MLR）中刺激强烈的同种异体反应性T细胞增殖。在体内，半同种异体DC有效地迁移至局部淋巴结，但在那里的存活时间不如自体DC长。此外，它们不能诱导针对靶肽的细胞毒性T淋巴细胞（CTL）活性，对过继转移的OT-II细胞的刺激也很弱。在同种异体耐受小鼠中，CD4(+)应答未改变，表明同种异体反应性T细胞应答不能为同时激活的抗原特异性应答提供帮助。在EL4肿瘤治疗模型中，用半同种异体DC/EL4融合杂种疫苗接种，但同种异体DC/EL4杂种疫苗接种则不能，显著提高了小鼠存活率。
半同种异体DC表达自身主要组织相容性复合体（MHC）可诱导抗原特异性免疫，但同时激活的同种异体旁观者应答不提供辅助或佐剂效应。
