Kenneth S. Tung
- Email: kst7k@virginia.edu
- Phone: 924-9194/5549
Primary Appointment
Professor, Pathology
Education
- MBBS, Medicine, Melbourne University, Melbourne, Australia
- Resident, Internal Medicine and Surgery, Melbourne University, Melbourne, Australia
- Resident, Pathology, Cleveland Clinic, Cleveland, Ohio
- Fellowship, Immunology, Scripps Clinic & Res. Fdn., La Jolla, CA
Research Disciplines
Cardiovascular Biology, Experimental Pathology, Immunology
Research Interests
Pathology
Research Description
Personal Statement
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.]
Selected Publications
Harakal J, Rival C, Qiao H, Tung KS, Regulatory T Cells Control Th2-Dominant Murine Autoimmune Gastritis., 2016; Journal of immunology (Baltimore, Md. : 1950). 197(1) 27-41. PMID: 27259856 | PMCID: PMC4912916
Rival C, Setiady Y, Samy ET, Harakal J, Tung KS, The unique neonatal NK cells: a critical component required for neonatal autoimmune disease induction by maternal autoantibody., 2014; Frontiers in immunology. 5() 242. PMID: 24904590 | PMCID: PMC4035566
Coquery CM, Loo WM, Wade NS, Bederman AG, Tung KS, Lewis JE, Hess H, Erickson LD, BAFF regulates T follicular helper cells and affects accumulation and IFNγ production in autoimmunity., 2014; Arthritis & rheumatology (Hoboken, N.J.). () . PMID: 25385309 | PMCID: PMC4342294
Coquery CM, Wade NS, Loo WM, Kinchen JM, Cox KM, Jiang C, Tung KS, Erickson LD, Neutrophils contribute to excess serum BAFF levels and promote CD4+ T cell and B cell responses in lupus-prone mice., 2014; PloS one. 9(7) e102284. PMID: 25010693 | PMCID: PMC4092127
Rival C, Wheeler K, Jeffrey S, Qiao H, Luu B, Tewalt EF, Engelhard VH, Tardif S, Hardy D, del Rio R, Teuscher C, Tung K, Regulatory T cells and vasectomy., 2013; Journal of reproductive immunology. 100(1) 66-75. PMID: 24080233 | PMCID: PMC3965253
Mauldin IS, Tung KS, Lorenz UM, The tyrosine phosphatase SHP-1 dampens murine Th17 development., 2012; Blood. 119(19) 4419-29. PMID: 22438258 | PMCID: PMC3362360
Tewalt EF, Cohen JN, Rouhani SJ, Guidi CJ, Qiao H, Fahl SP, Conaway MR, Bender TP, Tung KS, Vella AT, Adler AJ, Chen L, Engelhard VH, Lymphatic endothelial cells induce tolerance via PD-L1 and lack of costimulation leading to high-level PD-1 expression on CD8 T cells., 2012; Blood. () . PMID: 22993390 | PMCID: PMC3520619
Wheeler K, Tardif S, Rival C, Luu B, Bui E, Del Rio R, Teuscher C, Sparwasser T, Hardy D, Tung KS, Regulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy., 2011; Proceedings of the National Academy of Sciences of the United States of America. 108(18) 7511-6. PMID: 21502500 | PMCID: PMC3088630
Jiang C, Loo WM, Greenley EJ, Tung KS, Erickson LD, B cell maturation antigen deficiency exacerbates lymphoproliferation and autoimmunity in murine lupus., 2011; Journal of immunology (Baltimore, Md. : 1950). 186(11) 6136-47. PMID: 21536804 | PMCID: PMC3181142
Ernst PB, Wiznerowicz EB, Feldman SH, Tung KS, Pathogenesis of gastritis in ileitis-prone SAMP1/Yit mice., 2011; The Keio journal of medicine. 60(2) 65-8. PMID: 21720202
Ernst PB, Erickson LD, Loo WM, Scott KG, Wiznerowicz EB, Brown CC, Torres-Velez FJ, Alam MS, Black SG, McDuffie M, Feldman SH, Wallace JL, McKnight GW, Padol IT, Hunt RH, Tung KS, Spontaneous autoimmune gastritis and hypochlorhydria are manifest in the ileitis-prone SAMP1/YitFcs mice., 2011; American journal of physiology. Gastrointestinal and liver physiology. 302(1) G105-15. PMID: 21921286 | PMCID: PMC3345967
Carroll VA, Lundgren A, Wei H, Sainz S, Tung KS, Brown MG, Natural killer cells regulate murine cytomegalovirus-induced sialadenitis and salivary gland disease., 2011; Journal of virology. 86(4) 2132-42. PMID: 22156514 | PMCID: PMC3302420
Cohen JN, Guidi CJ, Tewalt EF, Qiao H, Rouhani SJ, Ruddell A, Farr AG, Tung KS, Engelhard VH, Lymph node-resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation., 2010; The Journal of experimental medicine. 207(4) 681-8. PMID: 20308365 | PMCID: PMC2856027
Case LK, Del Rio R, Bonney EA, Zachary JF, Blankenhorn EP, Tung KS, Teuscher C, The postnatal maternal environment affects autoimmune disease susceptibility in A/J mice., 2009; Cellular immunology. 260(2) 119-27. PMID: 19914609 | PMCID: PMC2795069
Guth A, Detanico T, Smith D, Tung KS, Bonorino C, Wysocki LJ, Spontaneous autoimmunity in mice that carry an IghV partial transgene: a required arginine in VHCDR3., 2009; Lupus. 18(4) 299-308. PMID: 19276297 | PMCID: PMC2892212
Wheeler KM, Samy ET, Tung KS, Cutting edge: normal regional lymph node enrichment of antigen-specific regulatory T cells with autoimmune disease-suppressive capacity., 2009; Journal of immunology (Baltimore, Md. : 1950). 183(12) 7635-8. PMID: 19923458 | PMCID: PMC2872190
Chavali AK, Gianchandani EP, Tung KS, Lawrence MB, Peirce SM, Papin JA, Characterizing emergent properties of immunological systems with multi-cellular rule-based computational modeling., 2008; Trends in immunology. 29(12) 589-99. PMID: 18964301
Samy ET, Wheeler KM, Roper RJ, Teuscher C, Tung KS, Cutting edge: Autoimmune disease in day 3 thymectomized mice is actively controlled by endogenous disease-specific regulatory T cells., 2008; Journal of immunology (Baltimore, Md. : 1950). 180(7) 4366-70. PMID: 18354156
Samy ET, Setiady YY, Ohno K, Pramoonjago P, Sharp C, Tung KS, The role of physiological self-antigen in the acquisition and maintenance of regulatory T-cell function., 2006; Immunological reviews. 212() 170-84. PMID: 16903914