Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Dept. of Surgery, University of Wisconsin, Madison, Wisconsin, United States of America.
PLoS One. 2014 Mar 19;9(3):e91274. doi: 10.1371/journal.pone.0091274. eCollection 2014.
Sex difference is an established risk factor for hematopoietic stem cell transplantation (HSCT)-related complications like graft versus host disease (GVHD). CD8pos cytotoxic T cells specific for Y chromosome-encoded minor Histocompatibility antigens (HY) play an important role therein. Prior to HSC donation, female donors may encounter HY antigens through fetomaternal or transmaternal cell flow, potentially leading to the induction of HY-specific cytotoxic or regulatory immune responses. Whether HY priming occurs independent of parity, and whether HY priming is dependent on the presence of male microchimerism, is as yet unknown.
We investigated the presence of HY-specific regulatory T cells (Treg) and male microchimerism in 45 healthy women with a fully documented pregnancy and family history. HY peptide-induced linked suppression, a commonly reported functional feature of CD4pos and CD8pos Treg, was measured by trans vivo Delayed Type Hypersensitivity testing. As source of HY antigens, male microchimerism was analyzed by real-time PCR and defined by the presence of male DNA in at least one purified leukocyte cell type.
HLA class I or class II restricted HY-specific Treg were detected in 26/42 (62%) women eligible for analysis. The prevalence of HY-specific Treg was significantly higher in women who had never given birth to sons than in women with male offspring (p = 0.004). Male microchimerism could be detected in 24 out of 45 (53%) women but did not correlate with the presence of HY specific Treg.
HY-specific Treg in women with male offspring have been described previously. Here we show for the first time that, in fact, HY specific Treg are more common in nulliparous women and in parous women with female offspring. Their presence is independent of the presence of male microchimerism. Whether HY-specific Treg presence in female stem cell grafts might decrease the GVHD incidence in male HSCT recipients needs to be investigated.
性别差异是造血干细胞移植（HSCT）相关并发症的既定危险因素，例如移植物抗宿主病（GVHD）。针对 Y 染色体编码的次要组织相容性抗原（HY）的 CD8pos 细胞毒性 T 细胞在此过程中发挥重要作用。在 HSC 捐赠之前，女性供体可能通过胎儿-母体或经母体细胞流动接触 HY 抗原，这可能导致 HY 特异性细胞毒性或调节性免疫反应的诱导。HY 启动是否独立于产次发生，以及 HY 启动是否依赖于男性微嵌合体的存在，目前尚不清楚。
我们研究了 45 名有完整妊娠和家族史的健康女性中 HY 特异性调节性 T 细胞（Treg）和男性微嵌合体的存在。通过活体 Delayed Type Hypersensitivity 测试测量了通常报道的 CD4pos 和 CD8pos Treg 的 HY 肽诱导的连锁抑制功能。作为 HY 抗原的来源，通过实时 PCR 分析男性微嵌合体，并定义为至少一种纯化白细胞细胞类型中存在男性 DNA。
在 42 名符合分析条件的女性中，检测到 26/42（62%） HLA Ⅰ类或Ⅱ类限制的 HY 特异性 Treg。从未生育过儿子的女性中 HY 特异性 Treg 的发生率明显高于有男性后代的女性（p=0.004）。可以在 45 名女性中的 24 名（53%）中检测到男性微嵌合体，但与 HY 特异性 Treg 的存在无关。
先前已经描述了有男性后代的女性中的 HY 特异性 Treg。在这里，我们首次表明，实际上，HY 特异性 Treg 在未生育的女性和有女性后代的多产妇中更为常见。它们的存在与男性微嵌合体的存在无关。女性干细胞移植物中 HY 特异性 Treg 的存在是否会降低男性 HSCT 受者的 GVHD 发生率，需要进一步研究。
