Claas F H, Roelen D L, van Rood J J, Brand A
Leiden University Medical Center, Dept. of Immunohaematology and Blood Transfusion, The Netherlands.
Transfus Clin Biol. 2001 Jun;8(3):315-7. doi: 10.1016/s1246-7820(01)00122-7.
Blood transfusions can induce both immune activation and immunosuppression. The former is expressed by the induction of HLA alloantibodies and T cell activation, while the latter is accompanied by enhanced graft survival in transfused versus non-transfused recipients. The immunological mechanism leading to downregulation of the alloimmune response has not yet been elucidated. Possible explanations include the induction of a Th2 response by non-professional antigen presentation by the transfused blood cells and blockage of alloreactive T cell reactivity by soluble HLA and soluble FasL in the supernatant of blood components. These mechanisms, however, do not explain the observations which have shown that the degree of HLA compatibility between the transfusion donor and patient is a determining factor. Transfusions in which the donor blood shares at least one HLA-DR antigen with the recipient induce tolerance, while fully HLA-DR mismatched transfusions lead to immunization. The importance of HLA-DR sharing suggests a central role for CD4+ regulatory T cells. In this case, indirect recognition of an allopeptide in the context of self-HLA-DR on the transfusion donor by CD4+ T cells of the recipient might be the clue to the induction of tolerance. Recent data from our laboratory in fact show that CD4+ T cells specific for an allopeptide in the context of self HLA-DR are able to downregulate the alloimmune response of autologous T cells. As these regulatory T cells produce IL-10, they may also be involved in the extension of tolerance via their modulatory effect on dendritic cells. It remains to be established whether these regulatory T cells are indeed responsible for the 'blood transfusion effect' in organ transplantation.
输血可诱导免疫激活和免疫抑制。前者表现为HLA同种抗体的诱导和T细胞激活，而后者则表现为输血受者与未输血受者相比移植存活率提高。导致同种免疫反应下调的免疫机制尚未阐明。可能的解释包括输血血细胞通过非专业抗原呈递诱导Th2反应，以及血液成分上清液中的可溶性HLA和可溶性FasL阻断同种反应性T细胞反应性。然而，这些机制并不能解释那些表明输血供体与患者之间HLA相容性程度是决定因素的观察结果。供体血液与受者至少共享一种HLA - DR抗原的输血可诱导耐受，而完全HLA - DR不匹配的输血则导致免疫。HLA - DR共享的重要性表明CD4 +调节性T细胞起核心作用。在这种情况下，受者的CD4 + T细胞在输血供体的自身HLA - DR背景下间接识别同种肽可能是诱导耐受的线索。事实上，我们实验室最近的数据表明，在自身HLA - DR背景下对同种肽特异的CD4 + T细胞能够下调自体T细胞的同种免疫反应。由于这些调节性T细胞产生IL - 10，它们也可能通过对树突状细胞的调节作用参与耐受的扩展。这些调节性T细胞是否确实是器官移植中“输血效应”的原因还有待确定。
