ImmunoTox Letter
performed his original tunes on the piano and voice.

English pages

The second day, the second special lecture wasReport from the holding of the 16th Annual
Meeting of the Japanese Society ofImmunotoxicology

presented by Dr. Masao Kosuge, the Director Emeritus

Takahiko Yoshida

The workshop focused on the immunotoxicological（Department of Health Science, Asahikawa Medical Collage）

testing methodology was chaired by Dr. Naohisa Tsutsuiof the Asahikawa Asahiyama Zoo entitled “The role of theAsahiyama Zoo in education and species preservation”.

focused on “Standardization of an immunotoxicity test:
The 16 Annual Meeting of the Japanese Society ofT cell-dependent antibody response to keyhole limpet

Immunotoxicology (JSIT) was held at Asahikawa CulturalHemocyanin”. Dr. Tsutsui started by mentioning

Hall in Asahikawa City with the theme of Children and“Background for a discussion on standardized protocols

Immunity during August 27-28, 2009. This meeting wasof KLH-TDAR”. Four cases were presented; “Rat strain

thhold by joint hosting with the 55th Meeting of Allergy andImmunotoxicology Scientific Committee / Japan Societyfor Occupational Health.
Dr. Dori R. Germolec (NIEHS, NIH, USA) presented thefirst special lecture entitled “Does immunomodulation
early in life increase disease risk in children andbeyond?”. The content of presentation was started
with basic animal studies and referred to the pointsof public health problems, and was also significant
as introduction to the symposium “Children andImmunity”. Symposia entitled, “Children and Immunity”
chaired by Drs. Fujio Kayama (Jichi Medical Collage)
and Dr. Kazuichi Nakamura (Shionogi PharmaceuticalCo.). The symposium featured presentations by Dr.
Sho Ishikawa (Tokyo University) on the breakdown ofmucosal immunity in the gut and allergic sensitization
by dioxins, Dr. Chisato Mori (Chiba University) on ahealth examination system to prevent fetal exposure topersistent organic pollutants and atopic dermatitis ininfants and Dr. Judith T. Zelikoff (New York Univ. USA)on the prenatal exposure to cigarette smoke increases
tumor susceptibility of juvenile mice via changes inanti-tumor mechanisms. The beginning of afternoon, theJSIT had the general assembly of this fiscal year. Thatevening, the reception had hosted at the Asahikawa
Grand Hotel. Dr. Nakamura reported on the progressof cooperation and scientific interchange between theJSIT and the Immunotoxicology Specialty Section ofSociety of Toxicology (ISS SOT). Then Dr. Judy Zelikoff
gave a greeting as the representative of ISS SOT. Bothscientific meetings of the 49th annual meeting of theSOT in Salt Lake City and the 17th annual meeting of theJSIT in Tsukuba City in 2010 were announced. Dr. Otsuki
─ 10 ─The 17th Annual Meeting of the JapaneseSociety of Immunotoxicology
September 9-10, 2010
Ohyama Memorial Hall,
National Institute for Environmental Studies
Theme: Immunotoxicology and Susceptibility
Invited Plenary Lecture:
Professor A Dean Befus (University of Alberta,CANADA)
Invited Special Lecture: Professor Kensuke Miyake(The Institute of Medical Science, The University ofTokyo)
Master’s Lecture: Jun-ichi Sawada, Ph.D. (President ofJSIT)
Symposium: “Immunotoxicity and chemical susceptibility”.
Invited Speaker: Mary Jane Selgrade, Ph.D. (USEPA)
Workshop
Oral/Poster presentation
Students session
President: Dr. Hidekazu Fujimaki
Research Center for Environmental Risk
Secretary office: Dr. Keiko Nohara
Environmental Health Sciences Division
National Institute for Environmental Studies
16-2, Onogawa, Tsukuba, Ibaraki 305-8506 Japan
Phone: 029-850-2500

FAX: 029-850-2574

e-mail: jsit17@nies.go.jp

Vol. 14 No. 2 (2009)
comparison of TDAR using KLH as an antigen” by Dr.

we were met by one of our hosts for this journey, Dr.

Ryota Kawai, “Protocol for rat KLH-TDAR in Takeda

Kazuichi Nakamura, who introduced us to Tokyo andPharmaceutical Company Limited” by Dr. Kanako Mori,

the wonders of Japanese noodle soup. On the 26th we“TDAR method using the commercial anti KLH-ELISA kit

joined Dr. Nakamura and a large group of JSIT members-Comparison with SRBC method-” by Hiroyuki Komatsu

for the flight from Tokyo to Asahikawa. Hokkaido is aand “Case study of both anti-KLH IgM and IgG antibody

volcanic island, and on our journey to Asahikawa wemeasurement in TDAR testing” by Hideki Harada.

were treated to spectacular mountain views and given a

Totally 22 oral and 13 poster presentations weretaste of the beautiful gardens that front local homes andsubmitted to the meeting and around 160 participants

farms. That evening we joined our hosts for the JSIT

spent fruitful opportunity and had enthusiastic discussion

conference opening dinner. Dr. Takahiko Yoshida, fromduring the sessions. The meeting was closed successfully

the Asahikawa Medical College and the President andwith hoping reunion in the next meeting.

Organizer of the 16th Annual Meeting, and the Executive
Committee welcomed us. The dinner was an excellent
opportunity for us to have superb Japanese cuisine anddiscuss current and future collaborations between theJSIT and the ISS.
Dr. Yoshida opened the meeting on Thursday morning,and the sessions began with oral presentations on theeffects of environmental chemicals on allergic andinfectious disease. In a session chaired by Dr. Yoshida,
Dr. Germolec presented the first special lecture of themeeting entitled “Does immunomodulation early in life
increase disease risk in children and beyond?” OralAt the welcoming reception. (From left to right)
Dr. Yoshida, Dr. Kayama, Dr. Germolec, Dr. Zelikoff, and Dr.
Kouchi.

presentations continued in the early afternoon in asession chaired by Dr. Yasuhide Kouchi and focused on
novel methods in immunotoxicity. The meeting theme
was highlighted in a symposium entitled, “Childrenand Immunity” chaired by Drs. Fujio Kayama andReport from the 16th Annual Meeting of theJapanese Society of Immunotoxicology

Dr. Kazuichi Nakamura. The symposium featured

1

Submitted by Dori Germolecand Judith Zelikoff 2

mucosal immunity in the gut and allergic sensitization by(1 National Institute of Environmental Health Sciences,to prevent fetal exposure to persistent organic pollutants

2

New York University Scholl of Medicine)presentations by Dr. Sho Ishikawa on the breakdown ofdioxins, Dr. Chisato Mori on a health examination system
and atopic dermatitis in infants and Dr. Judy Zelikoff,on how prenatal exposure to cigarette smoke increases

As part of the ongoing cooperation and scientifictumor susceptibility of juvenile mice via changes ininterchange that the Immunotoxicology Specialty Section

anti-tumor mechanisms. That evening, the JSIT hosted(ISS) has with the Japanese Society of Immunotoxicology,

a wonderful dinner reception at the Asahikawa Grand

Judy and I were chosen to represent the ISS at the 16th Annual

Hotel. We were fortunate that Dr. Takemi Otsuki wasMeeting of the Japanese Society of Immunotoxicology

willing to perform his “Song for the JSIT” which he(JSIT). The theme for this year’s meeting, held in thedebuted at an earlier JSIT meeting. It was a treat to see

beautiful city of Asahikawa on the Island of Hokkaido, wasold friends, begin new collaborations and hear about the“Children and Immunity”.

exciting plans for the sessions being planned for both

We arrived in Tokyo on the 25 of August and werethe 49th annual meeting of the SOT in Salt Lake City andwhisked to our hotel near the Haneda airport. There

the 17th Annual Meeting of the JSIT in Tsukuba nextth─ 11 ─ImmunoTox LetterSeptember.

A prize 年for annualconvention会 賞

The second day featured a special lecture chaired byDr. Jun-ichi Sawada and presented by Dr. Masao Kosuge,
the Director Emeritus of the Asahikawa Asahiyama Zoo

Development of a novel allergy test using acultured mast cell line

regarding the role of the Asahiyama Zoo in educationand species preservation. We were fortunate to get an

Ryosuke Nakamura, Yoshimi Uchida,
Masakazu Higuchi and Reiko Teshima“up close and personal” view of the zoo and all of its（Div. Novel Foods Immunochem., Natl. Inst. Health Sci., Tokyo, Japan）

inhabitants that afternoon. The afternoon Workshop
focused on “Standardization of an immunotoxicity test:

Rationale

T cell-dependent antibody response to keyhole limpet

Food allergy is a very popular disease among children,hemocyanin.” Oral and poster presentations highlighted

and the avoidance of causative foods is essential forthe outstanding contributions of our Japanese colleagues

children with allergies. However, inappropriate foodin all aspects of immunotoxicology.

avoidance can lead to nutritional deficits, especially

After the meeting, we were entertained by Dr. Yoshidain infants and children. The most reliable allergy test

who brought us up to the mountains for a visit tois an oral food challenge (OFC) test; however, in vivo

Daisetsuzan National Park and its volcanic hot springs,

tests are associated with a risk of possible anaphylaxis.

followed by a magnificent Japanese meal with many of

Ex vivo tests, such as the basophil-activation test, are

our meeting colleagues. Our flight back to Tokyo fromalso known to be effective; however, the basophil test

Asahikawa was just the beginning of another adventure,requires whole blood, which cannot be preserved forin which we traveled through the Ginza and up to thelengthy time periods. To detect allergen-specific IgE in

top of the Tokyo Tower. Dr. Nakamura acted as our toursera, solid-phase IgE-binding assays like the CAP test are

guide for a final day in Tokyo, where we saw the Great

commonly used. Although such immunochemical methods

Buddha of Kamakura, the port of Yokohama and its

are very sensitive, they frequently produce false-positive

magnificent Chinatown, as well as beautiful shrines andresults. The degranulation of human IgE receptor

temples, Our discussions on immunotoxicology and future(FcεRI)-transfected rat mast cell (RBL) lines seems to becollaborations did not end until we stepped on the planea possible indicator for human IgE, but the spontaneousheaded back to New York.

release of mediators from these cells in the presence ofWe would like to sincerely thank all of our hosts inhuman sera is not negligible.

Japan for their warmth, welcome and kindness. We
had many fruitful discussions about the future ofMethods

our Specialty Section and toxicology in general. The

We have established a new mast cell line, RS-ATL8,

hospitality that was extended to us was remarkable andthat has been stably transfected with human FcεRI genes

made our trip a never to be forgotten experience. Weand NF-AT-responsive luciferase gene. The cells werelook forward to continued collaborations with our JSIT

sensitized with a 1:100-dilution of sera from egg whitecolleagues.

allergy patients and then stimulated with a purified or
crude extract of egg white allergen. A two-fold increasein the luciferase level was adopted as a cut-off point.
The OFC tests were performed at the Fujita Health
University after obtaining informed consent.

ResultsSensitization with 15 pg/ml of IgE was sufficient todetect IgE Crosslinking-induced Luciferase Expression(EXiLE) using anti-IgE stimulation (data not shown).
Sera from a patient with egg white allergy diluted
─ 12 ─

Vol. 14 No. 2 (2009)
to at least 1:100 was suf ficient to elicit an EXiLE

A prize年
for encouragement
会 賞

reaction in RS-ATL8 cells without marked cytotoxicity,whereas a higher spontaneous release was observed

Analysis for suppressed expression ofNKp46 on NK cells exposed to asbestos,
possible predictive molecular marker foranti-tumor immune functionin the degranulation-based assay. The EXiLE results
were strongly correlated with the results of OFC
tests in patients with egg white allergy (P=0.001687,
Fisher’s exact test). The measured Max EXiLE andYasumitsu Nishimura1, Naoko Kumagai1,
Megumi Maeda1, Hiroaki Hayashi1,Takumi Kishimoto2 and Takemi Otsuki1

CAP test values were also strongly correlated (R=0.9127,
Spearman’s rank test).

（1Department of Hygiene, Kawasaki Medical School,Discussion

2Okayama Rosai Hospital）

Unlikely the degranulation-based mast cell activation

The present study tried to explore how expression

test, the EXiLE test was able to produce consistentof NKp46 on NK cells is suppressed by exposure toresults without inducing cytotoxicity. We observed

chrysotile B (CB) asbestos, as shown in our previousthat 1 fg/ml of egg antigen was sufficient to detect cell

report, and compared cytotoxicity of NK cells among

activation using the EXiLE test (data not shown). Of

pleural plaque-positive people with high or low expressionnote, the medium used here was supplemented with 10%of NKp46 and patient with mesothelioma, which wereFCS, which includes incredible amounts of non-specificassigned a score of 1, 2 and 3, respectively. NK cells

proteins, ensuring the robustness of the system.

in PBMCs cultured with CB showed a decrease in

Additionally, the EXiLE test and OFC test results wereNKp46 mRNA, whereas they show no accumulation ofstrongly correlated, whereas the correlation between

intracellular NKp46. The suppressed expression of NKp46

the OFC and CAP tests was not very good (P = 0.3684).

was also observed in NK cells in the culture insert over

The values of the Max EXiLE and CAP tests were also

the culture of PBMCs with CB. The cytotoxicity of NK

strongly correlated; therefore, the inconsistencies

cells was inversely correlated with the score determined

between the OFC and CAP test results reported herefor each patient-group. These results indicate thatmight be partly due to the excessive sensitivity of theexposure to asbestos causes suppressed expression ofCAP test. However, at least one serum, which contained

NKp46 at the mRNA level by alteration in production ofa high level (4.46 UA/ml) of egg white-specific IgE, did not

cytokines related with NK cell function, and suggest thatelicit an EXiLE reaction in RS-ATL8 cells. This patient

NKp46 might be a possible marker for anti-tumor immune

was also OFC negative. Therefore, the EXiLE test seems

function in people exposed to asbestos.

to be a promising in vitro IgE test for evaluating whether
IgE binding to an allergen is biologically meaningful.

Acknowledgements

An interim report about the guidanceon immunotoxicity for chemical risk
assessment discussed by WHO/IPCS
harmonization project

We are greatly honored to receive this prize for annualconvention. This study was supported by Grants-in-Aidfrom the Food Safety Commission, Japan (No.0708). We
are also grateful to Dr. Atsuo Urisu of Fujita Health

Reiko Teshima

University for his kind gift of the allergic patients’ sera.

（National Institute of Health Sciences）

WHO/IPCS harmonization project are now preparing
harmonized guidance for immunotoxicity risk assessmentfor chemicals. The Immunotoxicity drafting groupmeeting was held at the Netherland in April 2009. At themeeting, text of draft guideline (Chapter 1-7) and case─ 13 ─

ImmunoTox Letter
study report of platinum was discussed. In Next year
finalized draft document and several case study reports
will be public and peer reviewed.

─ 14 ─