当前位置: X-MOL 学术J. Clin. Invest. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A tribute to Terry Strom
The Journal of Clinical Investigation ( IF 15.9 ) Pub Date : 2018-02-05 , DOI: 10.1172/jci99905
Laurence A. Turka , Manikkam Suthanthiran

Terry Barton Strom, a giant in the field of transplantation immunology, died in Boston on December 20th, surrounded by friends and family, at the age of 76. He will be remembered by all whose path he crossed for his intellect and persona.

Terry grew up on the South Side of Chicago (more on that later) and went on to start his undergraduate studies at the University of Illinois. He entered medical school at the University of Illinois after his junior year, and — having never satisfied the foreign language requirement of the University — could not be awarded a bachelor’s degree. Thus, he was one of the rare physicians and academicians to have never graduated from college (although Harvard later awarded him a degree). This certainly did not hold him back. Following medical school, Terry was an intern in medicine at the University of Illinois and was then recruited to be a senior resident in medicine at the Beth Israel Hospital, after which he was renal fellow at the Peter Bent Brigham Hospital. On the completion of his clinical training, he worked in the lab of gentleman-scholar Charles (Bernie) Carpenter, entering and helping define the then nascent field of transplantation immunology. He was among the first and most distinguished of a long line of scientists to emerge from the Carpenter laboratory, the authors of this tribute include.

Following his formal laboratory training, Terry’s initial faculty appointment was at the Pent Brigham Hospital, and he later moved across the street to the Beth Israel Deaconess Hospital, where he stayed for the rest of his distinguished career. He established the Department of Immunology, rose through the ranks to become a Professor of Medicine and Surgery at Harvard Medical School, trained and mentored many fine scientists, and made numerous discoveries that have improved the lives of transplant recipients as well as patients with autoimmune diseases. A prolific author of almost 500 original articles, Terry’s seminal studies were models of clarity. For example, one of his early publications in the Proceedings of the National Academy of Sciences was the first description of cholinergic agents augmenting lymphocyte-mediated cytotoxicity (LMC), an effector mechanism central to the rejection of histoincompatible grafts (1). This original observation was rapidly amplified within a year by a publication in Science regarding the importance of microtubule integrity in LMC (2) and a publication in the Journal of Experimental Medicine regarding the counter-regulatory role of cyclic nucleotides on LMC (3). Yet another novel observation was the finding that insulin augmented LMC (published in Science) (4) followed by the demonstration of insulin receptors on alloimmune T cells (reported in the JCI) (5) that functioned as markers of activated T cells and B cells (reported in Nature) (6). These early studies foreshadow our current interest in T cell metabolism and identification of antigen-reactive cells via activation markers.

Terry’s preclinical investigations helped advance IL-2 receptor α (CD25) as a suitable target to prevent rejection in organ graft recipients, an idea that has been successfully translated to the clinic. Terry’s incisive studies have not only enabled clinical application of monoclonal antibodies, but have also improved our understanding of several immunosuppressive drugs currently used in the transplantation arena, including cyclosporine, glucocorticoids, and mTOR inhibitors.

Ever alert to promising inventions, Terry adopted the PCR assay to pioneer the characterization of intragraft gene expression patterns in preclinical transplantation models and, subsequently, in rejecting human allografts. In the spirit of “A man should look for what is and not for what he thinks should be,” Terry and his talented team unhesitatingly reported that acute rejection, previously considered a consequence primarily of graft-destructive immunity, is unexpectedly associated with the development of suppressor cells. Finally, a logical extension of this technology led to the exploration of peripheral blood gene expression patterns as biomarkers of allograft status.

Thus, Terry’s lab had a transformative impact in our understanding of transplant rejection and our goal of achieving transplant tolerance.

In recognition of his seminal contributions, Terry was honored by numerous awards, including election to the ASCI (almost 40 years ago), the Homer Smith Award of the American Society of Nephrology, the Starzl Prize in Surgery and Immunology, and the Established Investigator Award and Distinguished Achievement award, both from the American Society of Transplantation (AST). He is a past president of the AST and the founding president of Clinical Immunology Society. In recognition of his mentorship, Terry was awarded the AST Mentoring Award. Indeed, Terry is the recipient of every honor the AST can bestow on a transplant physician scientist. We had the privilege of collaborating with Terry in some of these studies and, like others who worked with him, admired his intellectual creativity and envied his ability to think outside the box. And not surprisingly, he was beloved by his patients.

The accomplishments above are truly impressive, but what those fortunate enough to know Terry will remember even more is his outsized personality. Terry was a character — there is no better word. He exuded boyish charm. With his full head of hair, gap-toothed smile, and large (6’4”) stature, he was a legend (see accompanying image). Befittingly, his son called him “Big T” and his brother called him “Zeus.” Growing up in a rough-and-tumble Polish neighborhood on Chicago’s South Side, Terry was the big Jewish kid — a target — but he learned to “give as good as he got.” He was also, by all accounts, a bad-ass kid. Those who had the privilege of knowing Terry as an adult will probably not be surprised that he was expelled from Hebrew school for throwing eggs at the rabbi. Or that, while serving in the Air Force (and it is truly hard to imagine Terry in the military), he did volunteer work for the Black Panthers. However, they might be surprised to learn that he had a life-time ban at the famed Drake Hotel on Michigan Avenue for serially crashing weddings, culminating in a food fight involving the wedding cake. At least that’s the legend, but if you knew Terry, you knew that it was eminently believable. And no one who knew Terry would be surprised that he was tremendously proud of these stories. He reveled in rising from humble beginnings to the peak of a lofty profession. And he loved being a rebel.

In addition to his intellectual talents, Terry was a gifted athlete. A rising high school football player, he and Dick Butkus were featured together in the local news. But two life-threatening subdural hematomas put an end to his athletic career. After recovering from surgery and emerging from a coma, his family and friends found him a changed man, no longer the prankster of earlier days. His lifelong friend Jon Borus refers to it as a “therapeutic/traumatic injury,” one that enabled him to focus his talents — and we are all better off for it.

While no longer a competitive athlete, Terry remained fiercely competitive. His children recall races in the park and hard-fought basketball games in the driveway that were always fun but were also training for life, where someone was always bigger and better, and you had better get used to it. In the halcyon days of postgraduate training when every minute of fellowship did not have be accounted for, one of the authors (identity intentionally concealed!) of this piece recalls very fondly spending several afternoons in Terry’s club playing what started as a friendly game of tennis and ending in a highly competitive brawl. A devoted fan, Terry thrilled in the success of Boston teams, but especially the Celtics. Among Terry’s many other hobbies, his love of wine and wine-making particularly stand out. He was especially proud that a dessert wine he had made one year with purchased grapes found its way onto the wine list of one of Boston’s finest restaurants. His friends also remember an exceedingly generous man — one who would take you into his home in hard times and be with you when you needed him.

An event that exemplifies Terry’s utmost humanism is one personally experienced by one of the authors of this tribute (M. Suthanthiran).

“On the first day of my transplant fellowship, I had to call Terry, my transplant attending, to seek his permission to return to Detroit Children’s Hospital to attend to my 9-year-old nephew, who had just been readmitted for a postoperative complication following total correction of Tetralogy of Fallot,” Suthanthiran said. “I was deeply concerned about making this request on my very first day of fellowship. Despite the unanticipated burden imposed on him by the sudden absence of the renal fellow on a very busy transplant service, Terry, without any hesitation whatsoever, said in the most caring voice, ‘Please, go and come back only when you feel comfortable.’”

Terry’s death was due to complications of an allogeneic stem cell transplant he received as part of his treatment for myelofibrosis (itself occurring as a complication of an earlier, and curative, autologous stem cell transplant for myeloma). He could have opted for maintenance transfusions but, instead, chose a riskier but potentially curative treatment. It reflected his tremendous optimism and joie de vivre, which were palpable to all he knew. One only had to be lucky enough to enjoy a meal or drink with friends at Terry and his wife Margot’s home in Brookline (where they lived together for almost 50 years) to see his spirit in action.

In many religions and belief systems, there is a variation of the aphorism that one must leave the world better than one finds it. Terry Strom — our brilliant mentor and dear friend — has most certainly not only enriched the field of immunobiology and transplantation, but also stimulated each of us to be better individuals.

Terry Strom was blessed with a wonderful family. The authors thank them — in particular his wife, Margot, and children, Adam and Rachel, — for sharing their memories of Terry. We join them in mourning his passing; we are all poorer for it.

Footnotes

Reference information: J Clin Invest. 2018;128(3):891–892. https://doi.org/10.1172/JCI99905.

References
  1. Strom TB, Deisseroth A, Morganroth J, Carpenter CB, Merrill JP. Alteration of the cytotoxic action of sensitized lymphocytes by cholinergic agents and activators of adenylate cyclase. Proc Natl Acad Sci U S A. 1972;69(10):2995–2999.View this article via: PubMedCrossRefGoogle Scholar
  2. Strom TB, Garovoy MR, Carpenter DB, Merrill JP. Microtubule function in immune and nonimmune lymphocyte-mediated cytotoxicity. Science. 1973;181(4095):171–173.View this article via: PubMedCrossRefGoogle Scholar
  3. Strom TB, Carpenter CB, Garovoy MR, Austen KF, Merrill JP, Kaliner M. The modulating influence of cyclic nucleotides upon lymphocyte-mediated cytotoxicity. J Exp Med. 1973;138(2):381–393.View this article via: PubMedCrossRefGoogle Scholar
  4. Strom TB, Bear RA, Carpenter CB. Insulin-induced augmentation of lymphocyte-mediated cytotoxicity. Science. 1975;187(4182):1206–1208.View this article via: PubMedCrossRefGoogle Scholar
  5. Helderman JH, Strom TB. Emergence of insulin receptors upon alloimmune T cells in the rat. J Clin Invest. 1977;59(2):338–344.View this article via: JCIPubMedCrossRefGoogle Scholar
  6. Helderman JH, Strom TB. Specific insulin binding site on T and B lymphocytes as a marker of cell activation. Nature. 1978;274(5666):62–63.View this article via: PubMedCrossRefGoogle Scholar


中文翻译:

致敬特里·斯特罗姆(Terry Strom)

移植免疫学领域的巨头特里·巴顿·斯特罗姆(Terry Barton Strom)于12月20日在波士顿去世,享年76岁。在他的家人和朋友的包围下,他将为他的智慧和个性所走过的一切路途所怀。

特里在芝加哥南区长大(稍后再介绍),然后在伊利诺伊大学开始他的本科学习。三年级后,他进入了伊利诺伊大学的医学院,而且,由于从未满足大学的外语要求,因此无法获得学士学位。因此,他是从未大学毕业的罕见医师和院士之一(尽管哈佛后来授予了他学位)。这当然并没有阻止他。医学院毕业后,特里是伊利诺伊大学的医学实习生,然后被聘为贝斯以色列医院的医学高级住院医师,之后他在彼得·本特·布里格姆医院(Peter Bent Brigham Hospital)担任肾脏研究员。完成临床培训后,他在绅士学者查尔斯(Bernie)Carpenter的实验室工作,进入并帮助定义了当时新生的移植免疫学领域。他是最早从Carpenter实验室出来的众多科学家中最杰出的科学家之一,此致谢的作者包括。

在接受了正式的实验室培训之后,Terry的最初任职是在Pent Brigham医院任教,后来他过马路搬到了Beth Israel Deaconess医院,在那里度过了他杰出的职业生涯。他成立了免疫学系,晋升为哈佛医学院的医学和外科教授,培训和指导了许多优秀的科学家,并取得了许多发现,这些发现改善了移植受者以及自身免疫性疾病患者的生活。特里的开创性研究是近500篇原始文章的多产作者,是清晰的模型。例如,他在《美国国家科学院院刊》上的早期出版物之一是胆碱能药物增强淋巴细胞介导的细胞毒性(LMC)的首次描述,该机制是排斥组织相容性移植物的核心效应器机制(1)。在一年内,《科学》杂志发表了一篇有关LMC中微管完整性的重要性的出版物,并在《实验医学杂志》上发表了有关环状核苷酸对LMC的反调节作用的出版物(3),这一原始观察结果在一年内迅速得到放大。另一个新发现是发现胰岛素增强的LMC(在《科学》上发表)(4),然后在同种免疫T细胞上证实了胰岛素受体(在JCI中报道)(5),该受体起活化T细胞和B细胞的标志物的作用。 (报告于自然)(6)。这些早期研究预示了我们当前对T细胞代谢和通过激活标志物鉴定抗原反应性细胞的兴趣。

特里的临床前研究帮助促进IL-2受体α(CD25)作为预防器官移植受体排斥反应的合适靶标,这一想法已成功地应用于临床。Terry的敏锐研究不仅使单克隆抗体的临床应用成为可能,而且还增进了我们对目前在移植领域使用的几种免疫抑制药物的了解,包括环孢霉素,糖皮质激素和mTOR抑制剂。

特里一直对有前途的发明保持警惕,因此采用PCR测定法率先在临床前移植模型中表征了移植物内部基因的表达模式,随后拒绝了人类同种异体移植物。特里和他的才华横溢的精神本着“一个人应该寻找的是而不是他认为的应该的”的精神,毫不犹豫地报告说,以前被认为主要是移植物破坏性免疫的结果的急性排斥反应与发育异常相关。抑制细胞的数量。最后,这项技术的合理扩展导致人们探索了外周血基因表达模式,将其作为同种异体移植状态的生物标记。

因此,Terry的实验室对我们对移植排斥的理解以及实现移植耐受性的目标产生了变革性的影响。

为表彰他的开创性贡献,特里是由无数的奖项兑现,其中包括当选ASCI(近40年前),肾病,在Starzl奖手术和免疫学的美国社会的荷马·史密斯奖和建立科学家奖以及美国移植学会(AST)颁发的杰出成就奖。他是AST的前任主席,也是临床免疫学会的创始主席。为了表彰他的指导,Terry被授予AST指导奖。确实,特里(Terry)是AST授予移植医学家科学家的所有荣誉的获得者。在其中的一些研究中,我们有幸与Terry合作,并且像其他与他一起工作的人一样,钦佩他的智力创造力并羡慕他跳出框框思考的能力。

上面的成就确实令人印象深刻,但是那些有幸认识特里的人会更加记得的是他的超大个性。特里(Terry)是个角色-没有比这更好的了。他散发出孩子气的魅力。满头的头发,露齿的微笑,高大的身材(6'4”),他是一个传奇人物(见附图)。恰如其分,他的儿子称他为“ Big T”,而哥哥则称他为“宙斯”。特里在芝加哥南边的一个波涛汹涌的波兰社区长大,他是犹太人的大孩子-一个目标-但他学会了“尽其所能”。众所周知,他还是个坏蛋。那些有幸认识特里成年的人可能不会感到惊讶,因为他因为在拉比扔鸡蛋而被希伯来学校开除。或者那个,在空军服役期间(很难想象特里在军队中服役),他为黑豹队做过志愿工作。但是,得知他因在密歇根大街上著名的德雷克酒店(Dreake Hotel)连续崩溃的婚礼而终生禁酒,最终导致涉及婚礼蛋糕的美食大战,他们可能会感到惊讶。至少那是传说,但是如果您认识Terry,就知道它是非常可信的。而且,没有一个知道特里的人会对他为这些故事感到骄傲而感到惊讶。他陶醉于从卑微的职业发展到崇高的职业的顶峰。而且他喜欢成为一名叛军。最后是一场涉及婚礼蛋糕的美食大战。至少那是传说,但是如果您认识Terry,就知道它是非常可信的。而且,没有一个知道特里的人会对他为这些故事感到骄傲而感到惊讶。他陶醉于从卑微的职业发展到崇高的职业的顶峰。而且他喜欢成为一名叛军。最后是一场涉及婚礼蛋糕的美食大战。至少那是传说,但是如果您认识Terry,就知道它是非常可信的。而且,没有一个知道特里的人会对他为这些故事感到骄傲而感到惊讶。他陶醉于从卑微的职业发展到崇高的职业的顶峰。而且他喜欢成为一名叛军。

除了他的智力天赋之外,Terry还是一位才华横溢的运动员。他和迪克·布特库斯(Dick Butkus)是一名正在崛起的高中足球运动员,并在当地新闻中脱口秀。但是有两次危及生命的硬膜下血肿终止了他的体育事业。从外科手术中恢复过来并摆脱昏迷后,他的家人和朋友发现他已经改变了,不再是以前的恶作剧。他的终身朋友乔恩·鲍鲁斯(Jon Borus)将其称为“治疗/创伤性伤害”,这使他能够集中精力发挥才华,我们为此而更好。

尽管不再是一名竞技运动员,但特里仍然保持着激烈的竞争。他的孩子们回想起在公园里的比赛和在车道上进行的艰苦的篮球比赛,这些比赛总是很有趣,但同时也为他们提供生活训练,在这里人们总是变得越来越大,越来越好,而你最好习惯了。在研究生训练的宁静时期,没有考虑到与团契的每一分钟,其中一位作者(特意隐瞒了身份!)回想起来非常愉快,他在特里的俱乐部度过了几个下午,玩起了一场友好的网球比赛并以激烈的竞争而告终。忠实的球迷,特里(Terry)对波士顿球队,尤其是凯尔特人队的成功感到兴奋。在特里的许多其他爱好中,他对葡萄酒和酿酒的热爱尤为突出。他为自己用购买的葡萄酿制的甜品酒被列入波士顿最好的餐厅之一的酒单而感到特别自豪。他的朋友还记得一个非常慷慨的人–一个会在困难时期将您带到他家中,并在您需要他时与您在一起的人。

一位纪念特里(M. Suthanthiran)的作者亲身经历了一场彰显特里最大人道主义的活动。

“在我获得移植奖学金的第一天,我不得不打电话给参加移植手术的特里打电话,寻求他的许可,让他返回底特律儿童医院去看望我的9岁侄子,后者刚刚因术后并发症再次入院。在全面校正了法洛四联症之后,” Suthanthiran说。“在团契的第一天,我非常担心提出此要求。尽管由于忙碌的移植服务突然缺肾而给他带来了意想不到的负担,但特里却毫不犹豫地说道:“请,只有在感到舒服的时候才能回来。” ”

特里之死是由于他接受了同种异体干细胞移植的并发症而导致的,这是他作为骨髓纤维化治疗的一部分(本身是骨髓瘤的早期治愈性自体干细胞移植的并发症)。他本可以选择维持性输血,但选择了风险更高但可能具有治愈作用的治疗方法。这反映了他的巨大乐观和活着的喜悦,这是他所知道的一切。一个人只需要幸运地在特里和他的妻子玛格特在布鲁克莱恩的家中(与他们一起生活了近50年)与朋友一起吃饭或喝水,就能看到他的精神。

在许多宗教和信仰体系中,格言的一种变化是,人们必须比发现的世界更好地离开世界。特里·斯特罗姆(Terry Strom)-我们的精明导师和亲爱的朋友-无疑不仅丰富了免疫生物学和移植领域,而且激发了我们每个人成为更好的个体。

特里·斯特罗姆(Terry Strom)拥有一个美好的家庭。作者感谢他们-特别是他的妻子玛格特(Margot)和孩子亚当(Adam)和雷切尔(Rachel)-分享了他们对特里的回忆。我们同他们一起哀悼他的逝世。我们都为此而贫穷。

脚注

参考信息:J Clin Invest。2018; 128(3):891–892。https://doi.org/10.1172/JCI99905。

参考
  1. Strom TB,Deisseroth A,Morganroth J,Carpenter CB,Merrill JP。胆碱能药物和腺苷酸环化酶激活剂改变致敏淋巴细胞的细胞毒性作用。美国国家自然科学委员会。1972; 69(10):2995–2999。查看此文章,网址为:PubMedCrossRefGoogle Scholar
  2. Strom TB,Garovoy MR,Carpenter DB,Merrill JP。微管在免疫和非免疫淋巴细胞介导的细胞毒性中起作用。科学。1973; 181(4095):171–173。查看此文章,网址为:PubMedCrossRefGoogle Scholar
  3. Strom TB,Carpenter CB,Garovoy MR,Austen KF,Merrill JP,KalinerM。环核苷酸对淋巴细胞介导的细胞毒性的调节作用。J Exp Med。1973; 138(2):381–393。查看此文章,网址为:PubMedCrossRefGoogle Scholar
  4. Strom TB,Bear RA,木匠CB。胰岛素诱导的淋巴细胞介导的细胞毒性增强。科学。1975; 187(4182):1206–1208。查看此文章,网址为:PubMedCrossRefGoogle Scholar
  5. Helderman JH,斯特罗姆·TB。大鼠同种免疫T细胞中胰岛素受体的出现。J临床投资。1977; 59(2):338–344。查看此文章,网址为:JCIPubMedCrossRefGoogle Scholar
  6. Helderman JH,斯特罗姆·TB。T和B淋巴细胞上的特定胰岛素结合位点是细胞活化的标志。大自然。1978; 274(5666):62–63。查看此文章,网址为:PubMedCrossRefGoogle Scholar
更新日期:2018-03-02
down
wechat
bug