Abstract

Regulation of Immune Response by Natural Killer T Cells

Masaki Terabe

Natural killer T cells (NKT cells) are T cells that recognize lipid antigens presented by class Ib major histocompatibility complex molecule CD1d. Although NKT cells constitute a small T-cell population, they play critical roles regulating immune responses in infections, autoimmune diseases and cancer. NKT cells have at least two subsets, based on the type of T-cell receptors (TCRs) expressed. Type I expresses a invariant TCRα chain utilizing Vα14Jα18 in mice (Vα24Jα18 in humans). Type II is defined as those that do not express the Vα14Jα18 TCRα chain. Type I NKT cells frequently facilitate, and type II NKT cells usually suppress, immune responses. The two types of NKT cells not only have opposing roles in immune regulation but also counteract each other, defining a new immunoregulatory axis. Changing the balance along this axis is key in manipulating immune responses. One way of tipping the balance is to activate one NKT cell type with an exogenous agonist. In fact, the type I NKT-cell agonist α-galactosylceramide (KRN7000) has been shown to induce strong tumor immunity in mice. However, it has some drawbacks, which may explain the limited success of KRN7000 in clinical trials. We recently discovered a new type agonist, β-mannosylceramide (β-ManCer), which induces tumor immunity by activating type I NKT cells, but through a different mechanism from that of KRN7000. Moreover, KRN7000 and β-ManCer synergized to induce tumor immunity. Overall, despite being a small part of the total T-cell population, NKT cells are attractive targets to manipulate the immune system to skew the response in a favorable direction.

International Relations of Keio Urology: History and Future Perspectives

Masaru Murai

The Department of Urology of Keio University School of Medicine was established in 1926, six years after the foundation of Keio University School of Medicine. This department was the third urological department to be established in Japan, following the departments of Jikei University and Kyusyu University, founded in 1922 and 1924, respectively. Keio Urology has been the most active urological department in Japan. After the 1960s, many urologists of Keio University School of Medicine studied urology abroad as residents and fellows, not only in the USA but also in Europe. Drs Akira Osawa, Hiroshi Tazaki, Yorio Naide and Hiroshi Nakamura were pioneers who followed in the footsteps of Dr Hideyuki Tohfukuji. These pioneers later became the chairpersons of many urological departments such as those at the National University of the Ryukyus, Keio University, Fujita Health University School of Medicine and the National Defense Medical College. Twelve urologists who graduated from Keio University before 1966 had experience of studying urology overseas. One hundred and one young urologists joined the Department of Urology at Keio University between 1967 and 1998, and 62 of these had the chance of studying urology abroad in the USA, France, England, Denmark or Sweden. Most of them spent more than two years as residents or fellows. Articles describing the scientific achievements of the Department have been published in many peer-reviewed international journals. In addition, many papers have been accepted for presentation at prestigious international conferences. Several international collaborative studies, such as the one on urothelial cancer, have been conducted with the collaboration of Keio. In my presentation, the history and future perspectives of Keio Urology will be presented, based on my experience as the fifth Chairman of the Department, as well as a Board Member of the Society of International Urology, Vice-Chair of International Consultation of Urological Diseases and past Secretary-General of the Urological Association of Asia. The future international development of the Department will be strongly emphasized, and the international outlook of our younger colleagues will be encouraged.