Zimmerer J M, Swamy P, Sanghavi P B, Wright C L, Abdel-Rasoul M, Elzein S M, Brutkiewicz R R, Bumgardner G L
Department of Surgery, Comprehensive Transplant Center, and the College of Medicine, The Ohio State University, Columbus, OH.
Am J Transplant. 2014 Nov;14(11):2491-9. doi: 10.1111/ajt.12922. Epub 2014 Sep 12.
We previously reported that posttransplant alloantibody production in CD8-deficient hosts is IL-4+ CD4+ T cell-dependent and IgG1 isotype-dominant. The current studies investigated the hypothesis that IL-4-producing natural killer T cells (NKT cells) contribute to maximal alloantibody production. To investigate this, alloantibody levels were examined in CD8-deficient WT, CD1d KO and Jα18 KO transplant recipients. We found that the magnitude of IgG1 alloantibody production was critically dependent on the presence of type I NKT cells, which are activated by day 1 posttransplant. Unexpectedly, type I NKT cell contribution to enhanced IgG1 alloantibody levels was interferon-γ-dependent and IL-4-independent. Cognate interactions between type I NKT and B cells alone do not stimulate alloantibody production. Instead, NKT cells appear to enhance maturation of IL-4+ CD4+ T cells. To our knowledge, this is the first report to substantiate a critical role for type I NKT cells in enhancing in vivo antibody production in response to endogenous antigenic stimuli.
我们之前报道过，CD8缺陷宿主中的移植后同种异体抗体产生依赖于IL-4+ CD4+ T细胞，且IgG1同种型占主导。当前研究调查了产生IL-4的自然杀伤T细胞（NKT细胞）促成最大程度同种异体抗体产生这一假说。为了对此进行研究，我们检测了CD8缺陷的野生型、CD1d基因敲除型和Jα18基因敲除型移植受者的同种异体抗体水平。我们发现，IgG1同种异体抗体产生的程度关键取决于I型NKT细胞的存在，这些细胞在移植后第1天就被激活。出乎意料的是，I型NKT细胞对增强IgG1同种异体抗体水平的作用依赖于干扰素-γ，而不依赖于IL-4。单独的I型NKT细胞与B细胞之间的同源相互作用并不会刺激同种异体抗体产生。相反，NKT细胞似乎会促进IL-4+ CD4+ T细胞的成熟。据我们所知，这是第一份证实I型NKT细胞在响应内源性抗原刺激增强体内抗体产生中起关键作用的报告。
