Identification of Human B-1 Helper T Cells With a Th1-Like Memory Phenotype and High Integrin CD49d Expression

Frontiers in Immunology

Hee Jung Jeon¹  Kook-Hwan Oh²  Dong Ki Kim²  Jaeseok Yang³  Tae Jin Kim⁴  Jung-Hwa Ryu⁵  Yixuan Xu⁶  Ji-Jing Yan⁶  Joon Young Jang⁶  Jae-Ghi Lee⁶  Taishi Fang⁶  Tai Yeon Koo⁶ 

[1] Department of Internal Medicine, Hallym University College of Medicine, Seoul, South Korea;Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea;Department of Surgery, Seoul National University Hospital, Seoul, South Korea;Division of Immunobiology, Sungkyunkwan University School of Medicine, Suwon, South Korea;Transplantation Center, Seoul National University Hospital, Seoul, South Korea;Transplantation Research Institute, Seoul National University College of Medicine, Seoul, South Korea;

关键词: antibody;    B-1 cell;    CD49d;    helper T cell;    memory phenotype;    Th1;   

DOI  :  10.3389/fimmu.2018.01617

来源: DOAJ

【 摘 要 】

Human B-1 cells have been proposed to be CD20+CD27+CD43+CD1c− B cells found in the umbilical cord and adult peripheral blood, but their regulatory mechanisms have not been well elucidated. Previously, we reported that mouse CD49dhigh CD4+ T cells could enhance the secretion of natural antibodies by B-1 cells. In this study, we aimed to investigate the presence and helper functions of the human equivalents of murine CD49dhigh CD4+ T cells. Here, we showed that human CD49dhigh CD4+ T cells found in the peritoneal cavity (PEC), spleen, and peripheral blood can enhance the production of IgM antibodies by B-1 cells. As revealed in mouse, CD49dhigh CD4+ T cells were more abundant in the PEC and showed a higher tendency to form conjugates with B cells than CD49dlow CD4+ T cells. Moreover, CD49dhigh CD4+ T cells showed a Th1-like memory phenotype, characterized by high expression of CD44 and CXCR3; low expression of CD62L and CCR7; rapid production of IFN-γ, tumor necrosis factor-α, and IL-2 upon stimulation with phorbol myristate acetate and ionomycin; and rapid proliferation upon stimulation with anti-CD3 and anti-CD28 antibodies. These cells also expressed high levels of PD-1, ICOS, and CD5, suggesting that they are undergoing chronic stimulation. Remarkably, CD49dhigh CD4+ T cells specifically helped B-1 cells, but not follicular memory B cells (CD27+ CD43−CD1c−) or marginal zone B cells (CD27+CD43−CD1c+), produce IgM and IgG antibodies. In parallel, the titer of human anti-blood group A IgM was positively correlated with the frequency of CD49dhigh CD4+ T cells. In conclusion, we identified human CD49dhigh CD4+ T cells with a Th1-like memory phenotype that secrete Th1 proinflammatory cytokines and help B-1 cells secrete antibodies, thereby aiding in primary defense. We suggest that these CD49dhigh CD4+ T cells are a unique type of B-cell helper T cells distinct from follicular helper T cells.

【 授权许可】

Unknown