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effect of mucosal route of administration of transgenic rice (Tg- rice)
seeds, which contain T-cell epitopes of Cryj1 and Cryj2, on murine
allergic rhinitis models and reported its clinical efficacy to actually
attenuate nasal symptoms. However, its mechanism remains to be
further investigatedandadverseevents of this therapeuticapproach
shouldbe very leastwithmore sophisticatedmanners.
Results:
Therefore, we have examined the effect of natural feeding
with protein bodies (PB) of transgenic rice seeds expressing
hypoallergenicwholeT cell epitopes of Cryj1andCryj2 (PB-Tg rice), in
comparisonwithwholeTg-rice, inamurinemodel of cedar pollinosis.
The numbers of sneezing after final intranasal challenge in mice
naturally fedwithPBTg-ricepowderwere significantly decreased ina
dosedependentmanner,withlessdoses,incomparisonwiththoseof
whole Tg-rice powder. Histopathological findings correspondingly
demonstrated that the number of eosinophils infiltrating into nasal
mucosa decreased and the damage of epithelial cells was less found
in each group of mice. Sublingual route of administration is also
effective to attenuate nasal symptoms.
Conclusion:
Protein body fraction of Tg-rice more efficiently
downregulated nasal symptom in murine model of cedar pollinosis
with natural feeding or sublingual administration. These result
implicates that intake of protein body form of Tg-rice can be more
promising strategy and material to be utilized for mucosal route of
immunotherapy to attenuate nasal symptoms of patientswith cedar
pollinosis.
Enhancement of NK cell-mediated cytotoxicity during chronic
virus infection
Ha, S.-J., Oh,J.
YonseiUniversity,DepartmentofBiochemistry,Seoul,Korea,Republicof
NK cells are critical for the clearance of parasites, virus-infected
cells and tumors. Recently, several groups reported that NK cells
could control virus-specific T cell responses at early stage of chronic
infection. However, the physiological role of NK cell in a host infected
with chronic virus has not been extensively studied. To identify the
role of NK cell in chronic virus infection was studied in the mice
persistently infected with LCMV-CL13. In this study, we found that
terminally differentiated CD27
low
KLRG1
+
CD11b
high
NK cells were
more abundant in the chronically infected mice than in naïve mice.
Furthermore, the NK cells from CL13-infected mice were shown to
express higher level of an activating receptor, NKG2D and lower
levels of the inhibitory receptors, NKG2A and Ly49C/I than those
from naïve mice. Such an integrative signal seemed to enhance
NK cell activity, elevating expressions of CD69 and Granzyme B.
At the functional level, NK cells in the CL13-infected mice display
increased
exvivo
IFN-γ production and increased
invitro
cytotoxicity.
Indeed, the CL13-infected mice, but not naive mice, dramatically
delayed tumor formation when various tumor cells such as TC-1
lung adenocarcinoma and B16F10 melanoma were inoculated. The
significant decrease of tumor promotion in CL13-infected mice was
abrogated by depletion of NK cells, suggesting NK cell-mediated
cytolytic activity for tumors. Currently, we are investigating which
molecular are able to empower NK cells with enhanced cytolytic
activity. Discovery of the key regulator for the enhanced activity of
NK cell could be a potent cancer drug.
CD169 identifies an anti-tumor macrophage subpopulation in
human hepatocellular carcinoma
Wu, Y., Zhang, Y., Zheng, L.
SunYat-senUniversity,Guangzhou,China
Macrophages are a major component of most solid tumors and
can exert both anti- and pro-tumorigenic functions. Although the
immunosuppressive/pro-tumor roles of macrophages have been
widely examined, significantly less is known about macrophage
subpopulationsthathavepotentialanti-tumorpropertiesinhumans.
In the present study, a population of CD169
+
macrophages with
relatively high expression levels of HLA-DR and CD86 was identified
inhumanhepatocellular carcinoma tissues.The frequencyofCD169-
expressing macrophages within cancer nests was significantly
lower compared with that found in paired non- tumor areas.
In vitro
experiments revealed that in the presence of anti-CD3 stimulation,
CD169
+
macrophages could significantly enhance the proliferation,
cytotoxicity, and cytokine production capacity of autologous CD8
+
T cells in a CD169 molecule- dependent manner. Autocrine TGF-β
produced by tumor-stimulated macrophages was involved in the
down-regulation of CD169 expression on these cells. Moreover,
CD169
+
macrophage accumulation in tumor tissues was negatively
associatedwithdisease progressionandpredictedfavorablesurvival
in hepatocellular carcinoma patients, which was in contrast to the
trend observed for total CD68
+
macrophages. Therefore, CD169may
act as a costimulatory molecule for cytotoxic T cell activation, and
could define a population of tumor-infiltrating macrophages with
potential anti-tumor properties in human hepatocellular carcinoma
tissues.
All the authors declare no competing financial interests and concur
with the submission.
Combination of TLR2 and TLR3 ligands enhances maintenance
of CD4 T cells and production of class-switched antibody
Ha, S.-J.
1
, Lee, B.R.
1
, Jeong, S.K.
2
, Ahn, B.C.
2
, Shin, S.J.
3
, Yum, J.S.
2
1
YonseiUniversity,DepartmentofBiochemistry,Seoul,Korea,Republic
of,
2
CHAVaccineInstitute,R&DCenter,Seongnam-si, Korea,Republicof,
3
InstituteforImmunologyandImmunologicalDiseases,BrainKorea21
PLUSProjectforMedicalScience, YonseiUniversityCollegeofMedicine,
DepartmentofMicrobiology,Seoul,Korea,Republicof
The efficacy of the vaccines in numerous studies including
priming or boosting regimens for prophylactic purpose as well
as its therapeutic application depends on the type of adjuvant.
Thus, a better understanding on the combination of different
type adjuvants is essential for optimal immune responses. Here,
we investigated the mechanistic actions of a combined adjuvant
Pam3csk4 and PolyI:C (hereafter referred to as L-pampo) to improve
the adjuvanted-vaccine efficacy. Notably, an administration of
ovalbumin (OVA) with L-pampo induced the enhanced production
of antibody, correlated to reciprocal expansions of germinal center B
cells andmulti-functional CD4T cells concomitantly producing IFN-γ
andTNF-α in an antigen-specificmanner after tertiary immunization
with OVA. To dissect the precise mechanism for the synergy by
TLR2 and TLR3 ligands in L-pampo, we subdivided courses of the
immune responses after primary immunization into three different
phases. During 24 hrs after immunization, unlike PolyI:C alone,
the levels of type I IFN in serum and spleen selectively decreased