Huang Yafei, Heiser Ryan A, Detanico Thiago O, Getahun Andrew, Kirchenbaum Greg A, Casper Tamara L, Aydintug M Kemal, Carding Simon R, Ikuta Koichi, Huang Hua, Cambier John C, Wysocki Lawrence J, O'Brien Rebecca L, Born Willi K
Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
Department of Immunology & Microbiology, University of Colorado Health Sciences Center, Aurora, CO 80045;
Proc Natl Acad Sci U S A. 2015 Jan 6;112(1):E39-48. doi: 10.1073/pnas.1415107111. Epub 2014 Dec 22.
γδ T cells can influence specific antibody responses. Here, we report that mice deficient in individual γδ T-cell subsets have altered levels of serum antibodies, including all major subclasses, sometimes regardless of the presence of αβ T cells. One strain with a partial γδ deficiency that increases IgE antibodies also displayed increases in IL-4-producing T cells (both residual γδ T cells and αβ T cells) and in systemic IL-4 levels. Its B cells expressed IL-4-regulated inhibitory receptors (CD5, CD22, and CD32) at diminished levels, whereas IL-4-inducible IL-4 receptor α and MHCII were increased. They also showed signs of activation and spontaneously formed germinal centers. These mice displayed IgE-dependent features found in hyper-IgE syndrome and developed antichromatin, antinuclear, and anticytoplasmic autoantibodies. In contrast, mice deficient in all γδ T cells had nearly unchanged Ig levels and did not develop autoantibodies. Removing IL-4 abrogated the increases in IgE, antichromatin antibodies, and autoantibodies in the partially γδ-deficient mice. Our data suggest that γδ T cells, controlled by their own cross-talk, affect IL-4 production, B-cell activation, and B-cell tolerance.
γδ T细胞可影响特异性抗体反应。在此，我们报告，单个γδ T细胞亚群缺陷的小鼠血清抗体水平发生改变，包括所有主要亚类，有时与αβ T细胞的存在无关。一种部分γδ缺陷且IgE抗体增加的品系，其产生IL-4的T细胞（残余γδ T细胞和αβ T细胞）及全身IL-4水平也增加。其B细胞表达的IL-4调节抑制性受体（CD5、CD22和CD32）水平降低，而IL-4诱导的IL-4受体α和MHCII增加。它们还表现出活化迹象并自发形成生发中心。这些小鼠表现出高IgE综合征中发现的IgE依赖性特征，并产生抗染色质、抗核和抗细胞质自身抗体。相反，所有γδ T细胞缺陷的小鼠Ig水平几乎未变，且未产生自身抗体。去除IL-4可消除部分γδ缺陷小鼠中IgE、抗染色质抗体和自身抗体的增加。我们的数据表明，γδ T细胞受自身相互作用的控制，影响IL-4产生、B细胞活化和B细胞耐受性。
