(1) Yoshihiro Asano
Department of Immunology,
Faculty of Medicine,
University of Tokyo,
Associate Professor, M.D. and Ph.D.
SPONSOR AND HOST INSTITUTION:
Dr. Richard J Hodes
Director, National Institute on Aging
Dr. Alfred Singer
Chief, Experimental Immunology Branch
National Cancer Institute
DATES OF VISITS: March 16-21 1995
SUMMARY OF ACTIVITIES:
March 16-21 1995: Keystone Symposia on Molecular and Celluar Biology “Control and Manipulation of Immune Response”
March 23 - 27 1995: National Institute on Aging, and National Cancer Institute/ Experimental Immunology Branch
Immune response is mediated by a set of immunocompetent cells and regulated by cell-cell interaction between subsets of the cells. We established a number of IL2 dependent T cells clones with a definite suppressor function for the antibody response. The activated CD4+ suppressor T(Ts) cells could inhibit the increase of intracellular Ca2+ of helper T(Th) clones induced by antigen-pulsed antigen presenting cells. A strict was found in the suppressive activity of Ts clones in that Ts clones could suppress the Ca2+ responses of Th1 or Th2 clones but not of other CD4+ Ts clones. Ts clones could suppress the Ca2+ influx of Th clones induced only by antigen-pulsed APC or anti-TcR antibody but not by ConA or IL2. Ts clones released soluble immunosuppressive factors upon stimulation with immobilized anti-CD3 antibody. These results indicate that Ts clones inhibit the early signal transduction of Th cells nd thus suppressing specific unmune responses.
To understand the mechanism of the suppression, we are now trying to identify the molecule with suppressive activity on Th cells using chemical and molecular technology. During this visit, I discussed the results of our recent studies and future collaborative studies with Drs. R. J. Hodes and A. Singer and other active scientists of the field. In addition, Dr. Singer and I agreed with starting a collaborative study analyzing a new cell surface receptor molecule which transduces a negative signal for TcR-mediated T cell stimulation.
On the way to the National Institutes of Health, Bethesda, I participated in the Keystone Symposia on Molecular adn Cellular Biology “Control and Manipulaiton of the Immune Response” held in Taos, New Mexico. The theme of this symposium was closely related to my research interest and a number of leading scientists of the field were attended the symposium. It provided me a nice opportunity to discuss and exchange idas with many scientists working in the field, and it was indeed very informative.
(2) Hiromi Fujiwara
Biomedical Research Center,
Osaka University Medical Shool
Associate Professor
SPONSOR AND HOST INSTITUTION:
Dr. Richard Hodes,
National Institutes of Health
DATES OF VISIT: September 25 - October 9, 1995
SUMMARY OF ACTIVITIES:
A. Objectives of this study
I visited the following institutes/universities.
l) Washington University Medical School, St. Louis, MO (Drs. Robert Schreiber, Osami Kanagawa, and Jun Shimizu)
2) National Institutes of Health, Bethesda, MD (Drs. Richard Hodes, Alfread Singer, and Yutaka Kawakami)
3) The Wistar Institute, Philadelphia, PA (Dr. Georgio Trinchieri)
4) Dana Farbar Cancer Institute, Boston, MA (Drs. Steven Burakoffand Shigeo Koyasu)
5) Genetics Institute, Cambridge, MA (Drs. Steven Herrmann and Michiko Kobayashi)
The main purpose of this visit was to present our recent results obtained regarding the modulatory effects of various cytokines (IL-12 and IL-6) on T cell responses to researchers listed above, discuss with them based on our results, and promote collaborative work.
B. Achievements and relation of this study to future work
l) Seminar or data presentations
At Washington Univ. Med Sch and Genetics Institute, I gave a formal seminar entitled “rIL-12 administration induces complete tumor regession: Response is correlated with a striking reversal of suppressed IFN-!
!!Production by anti-tumor T cells”. I also performed an informal presentation of the above work at other institutes. 2) Discussion and information exchange
Since IL-12 was discovered in 1989, this cytokine has been given attention due to it’s bioactivities including the effect on the development and activation of the T cell and/or NK cell. It is also increasingly evident that IL-12 and its related cytokines such as IFN-!
!!and IL-6 have a critical role in modulating immune responses of the T cell including anti-tumor T cell responses. I discussed with Drs. Schreiber and Herrmann concerning the effect of IL-12 on IFN-!
!!Production by T cell and NK cells as well as molecular mechanisms underiying IFN-Y-induced suppression of tumor cell growth. IL-12 is known to be produced by macrophages during T cell-macrophage (antigen-presenting cell) interactions. I discussed with Drs. Trichleri and Singer regarding the regulatory mechanisms of IL-12 production.
Additional discussions were made with other researchers in the context of how to measure the migration of activated T cells to inflammatory lesions, anti-retrovirus effect of IL-12, and the role of costimulatory molecules in the induction of IL-2R expression.
All information obtained through discussion could contribute to our ongoing and future work which investigates the anti-tumor effect of IL-12.