Kenneth S. K. Tung,
M.D.
Professor, Renal
Pathology
EDUCATION:
Medical School: Melbourne University, 1959,
M.B.B.S.
Internship: Cleveland Clinic, Intern, 1962
Residency: Cleveland Clinic, Anatomical and Clinical
Pathology 1963 - 1967
Fellowship: Fellowship in Immunology. Scripps Clinic
and Research Foundation, 1968 - 1970
CLINICAL:
Renal immunopathology
RESEARCH:
Tolerance and Autoimmunity: My laboratory explores the fundamental
mechanisms of prevention and induction of autoimmune disease of
clinical relevance, under four major topics. First, we
investigate how Ag specific regulatory T cells bearing Foxp3 (Treg)
control physiological self tolerance in normal mice. We
discovered that regional lymph nodes of normal mice accumulate highly
active Treg that suppress autoimmunity of the organ draining to it. We
now want to know whether in this strategic location, Treg maintain self
tolerance by preventing autoimmune disease triggered by endogenous
“danger signal”. Second, we study sperm granuloma in
unilaterally-vasectomized mice as endogenous “danger signal”.
Unexpectedly, vx mice develop tolerance to testis Ag, which is
terminated by depletion of Treg, leading to severe testis autoimmune
disease. We want to know how Treg normally control the choice
between tolerance and autoimmune pathogenesis in autoimmune
response. [The project is clinically relevant and of global
significance, since the annual rate of vasectomy in the US alone is 0.5
million and rising.] Third, we developed a model of
spontaneous autoimmune disease in a mice expressing transgenic
ovalbumin as male germ cell autoantigen and transgenic TCR specific for
OVA peptide. [The model elucidates how human autoimmune diseases
progress from preclinical to clinical stage, from remission to relapse,
and design of appropriate therapy.] We discovered that
transferred autoantibody rapidly forms immune complexes with OVA,
which, contrary to current dogma, is not sequestered behind the
blood-testis barrier. The immune complexes attract and activate
Ag presenting cells and Ag specific T cells in a unique testis
micro-environment, expanding pathogenic Th17 cells. We want to
know the molecular mechanisms responsible for the events.
Fourth, we discover that maternal autoantibody, nonpathogenic in
adults, induces pathogenic innate response, as well as de novo
pathogenic T cell response in the progeny, leading to severe neonatal
autoimmunity. Notably, antibody needs to reach the pups within
but not beyond, the first 5 days of life. We found that the
neonatal propensity for autoimmune disease is explicable by the
functional supremacy of neonatal NK cell and FcgRIII+ cells over adult
counterparts. [This is a model of congenital heart block: a
serious human disease that occurs in the newborn of mothers suffering
from Sjogren’s disease, a type of lupus.]
REFERENCES:
- Samy ET, Wheeler KM, Roper RJ,
Teuscher C, Tung KSK. Cutting Edge: Autoimmune
disease in day 3-thymectomized mice is actively controlled by
endogenous disease-specific regulatory T cells. J
Immunol 180: 4366-70, 2008.
- Ruan
QG, Tung K, Eisenman D, Setiady Y, Eckenrode S, Yi B,
Zheng WP, Zhang Y, Peltonen L and She J-X. The autoimmune regulatory
(Aire) directly controls the expression of genes critical for thymic
epithelial function. J Immunol. 178:7173-80,
2007.
- Samy ET, Setiady YY, Tung
KSK. Regulatory T cells in acquisition and maintenance of self
tolerance. Immun. Rev. 212:170-184,
2006.
- Setiady YY,
Ohno K, Samy ET, Bagavant H, Qiao H, Sharp C, She JX, Tung
KSK. Physiological self antigens rapidly capacitate autoimmune
disease-specific polyclonal CD4+CD25+ regulatory T cells.
Blood 107: 1056-1062,
2006.
- Samy ET, Parker LA, Sharp CP, Tung
KSK. Continuous control against spontaneous autoimmunity
in regional lymph nodes by CD4+CD25+ regulatory T cells.
J. Exp. Med. 202: 771-781,
2005.
A list of Dr. Tung's journal publications can be obtained from
PubMed.
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