期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：1
页码：E39-E48
DOI：10.1073/pnas.1415107111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThis study changes our understanding of the relationship between T cells and B cells. Although it is known that T cells provide help for specific B-cell responses, it is unclear if and to what extent T cells also influence preimmune B-cell functions. We show here that {gamma}{delta} T cells modulate systemic antibody levels in nonimmunized mice, including all major subclasses and especially IgE antibodies. One mouse strain deficient in certain {gamma}{delta} T cells developed various autoantibodies, whereas mice deficient in all {gamma}{delta} T cells had relatively normal antibodies. Based on these and other findings, we conclude that {gamma}{delta} T cells, influenced by their own cross-talk, affect IL-4 production, B-cell activation, and B-cell tolerance. {gamma}{delta} T cells can influence specific antibody responses. Here, we report that mice deficient in individual {gamma}{delta} T-cell subsets have altered levels of serum antibodies, including all major subclasses, sometimes regardless of the presence of {beta} T cells. One strain with a partial {gamma}{delta} deficiency that increases IgE antibodies also displayed increases in IL-4-producing T cells (both residual {gamma}{delta} T cells and {beta} 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 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 {gamma}{delta} 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 {gamma}{delta}-deficient mice. Our data suggest that {gamma}{delta} T cells, controlled by their own cross-talk, affect IL-4 production, B-cell activation, and B-cell tolerance.
