Participating Faculty
William C. Davis

Professor
Veterinary Microbiology & Pathology
Washington State University
Pullman, WA 99164- 7040

Ph.D., 1967
Medical Microbiology Transplantation Immunology
Stanford University, Palo Alto, CA

Phone: 509-335-6051
Fax: 509-335-8529
Email: davisw@wsu.edu

Research Interests:
Immunology, Immunopathology, Immunogenetics, Infectious diseases

Research Summary:

The long term objectives of our research program are to elucidate the mechanisms regulating the immune response to infectious agents and develop protective vaccines. To achieve these objectives, we continue to develop and use monoclonal antibodies and assays to study the immune response in domestic animals with a primary focus on ruminants. M. avium subsp. paratuberculosis (Map) has been selected as the model pathogen for our investigations because of its economic importance and its potential for providing insight into the mechanisms regulating the immune response to Map and other intracellular pathogens. Map is the causative agent of Johne’s disease, paratuberculosis (Ptb), a chronic wasting disease of the intestine. It causes significant economic loss to producers, especially the dairy industry, due to increase in forage consumption, decreased milk production and early culling due to poor health of affected animals. There is also a concern that Map is a zoonotic pathogen. Map has been isolated from human patients with Crohn’s disease, an iliocolitis. It is not clear whether Map is the etiologic agent causing Crohn’s disease or that patients with Crohn’s disease are essentially unfortunate sentinels signaling the prevalence of Map in the food stream and water supply.
The disease has been difficult to control because of the lack of sensitivity and specificity of available diagnostic assays, lack of an efficacious vaccine, and the existence of wildlife reservoirs that make eradication difficult. To address these problems, we have developed a latex bead assay for the differential diagnosis of bovine tuberculosis (Btb) and paratuberculosis (Ptb). The assay has been validated for Btb. Efforts are underway to identify antigens for use in diagnosis of Ptb. A calf model has been developed to study the immune response to Map, using multi-color flow cytometry assay. The initial studies have shown a consistent CD4 and CD8 memory T (mT) cell proliferative response can be detected to PPD and soluble antigens. The role of NK cells and __ T cells in innate immunity to Map is unclear.
The working hypothesis is:
Dendritic cells play a central role in the development and maintenance of protective immunity against Map. The specific objectives to test the hypothesis are:
1) Determine how Map affects DC maturation and secretion of regulatory cytokines and chemokines in vitro.
2) Detail the primary CD4 and CD8 T cell immune responses mediated by immature DC (iDC) and matured DC (mDC) following exposure to different antigenic stimuli in vitro.
3) Determine if regulatory DC (DCr) and regulatory T cells (Tr) play a role in modulating the immune response to Map.
4) Compare the capacity of iDC, primed with wild type or deletion mutant strains of Map or with expressed Map antigens, to elicit cell mediated and humoral responses in vivo.

Representative Publications:
Stone DM, Norton LK, Davis WC. Spontaneously proliferating lymphocytes from bovine leukemia virus-infected, lymphocytotic cattle are not the virus-expressing lymphocytes, as these cells remain in G0/G1 of the cell cycle progression and are protected from apoptosis. J Gen Virol 81:971-981, 2000.

Davis WC, Heirman LR, Hamilton MJ, Parish S, Barrington GM, Loftis A, Rogers M. Flow cytometric analysis of an immunodeficiency disorder affecting juvenile llamas. Vet Immunol Immunpathol 74:103-120, 2000.

Baumgartner M, Chaussepied M, Moreau M-F, Werling D, Davis WC, Garcia A, Langsley G. Constitutive PI3-K activity is essential for proliferation, but not survival, of Theileria parva-transformed B cells. Cell Microbiol 2:329-339, 2000.

Valdez RA, McGuire TC, Brown WC, Davis WC, Knowles DP: An in vivo model to investigate lymphocyte-mediated immunity during acute hemoparasitic infections: use of a monoclonal antibody to selectively deplete CD4+ T lymphocytes from thymectomized calves. Annals New York Acad. Sci 916:233-36, 2000.

Davis WC, Khalid AM, Hamilton MJ, Ahn JS, Park YH, Cantor GH. The use of crossreactive monoclonal antibodies to characterize the immune system of the water buffalo (Bubalus bubalus). J Vet Sci 2:103-109, 2001.

Lee SU, Ferens W, Davis WC, Hamilton MJ, Park YH, Katazyna Dziewanowska K, Fox LK, Naessens J, Bohach GA. Activation molecule (ACT3) expressed on superantigen stimulated cells is CD26. J Infect Immun 69:7190-7193, 2001.

Davis WC, Haverson K, Saalmüller A, Yang H, Lunney JK, Hamilton MJ, Pescovitz MD. Analysis of monoclonal antibodies reacting with molecules expressed on ?? T cells. Vet Immunol Immunopath 80:53-62, 2001.

Konno A, Ahn J-S, Kitamura M, Hamilton MJ, Gebe JA, Aruffo A, Davis WC. Tissue distribution of CD6 and CD6-ligand in cattle: Expression of the CD6-ligand (ALCAM, CD166) in the autonomic nervous system of cattle and humans. J Leuk Biol 69:944-950, 2001.

Davis WC, Khalid AM, Hamilton MJ, Ahn JS, Park YH, Cantor GH. The use of crossreactive monoclonal antibodies to characterize the immune system of the water buffalo (Bubalus bubalus). J Vet Sci 2:103-109, 2001.

Ebling TL, Fox LK, Bayles KW, Bohach GA, Byrne KM, Davis WC, Ferens WA, Hillers JK. Bovine mammary immune response to an experimental intramammary infection with a Staphylococcal aureus strain containing a gene for staphylococcal enterotoxin C1. J Dairy Sci 84:2044-2050, 2001.

Lee SU, Ferens W, Davis WC, Hamilton MJ, Park YH, Katazyna Dziewanowska K, Fox LK, Naessens J, Bohach GA. Activation molecule (ACT3) expressed on superantigen stimulated cells is CD26. J Infect Immun 69:7190-7193, 2001.

Herrmann LM, Davis WC, Knowles DP, Wardrop J, Sy M-S, Gambetti P, O’Rourke K. Cellular prion protein is expressed in peripheral blood mononuclear cells but not platelets of normal and scrapie-infected sheep. Haematologica 86:146-153, 2001.

Haverson, K, Saalmüller, A, Alvarez, B, Alonso, F, Bailey, M, Bianchi, ATJ, Boersma, WJA, Chen, Z, Davis, WC, Dominguez, J, Engelhardt, H, Ezquerra, A, Grosmaire, LS, Hamilton, MJ, Hollemweguer, E, Huang, CA, Khanna, KV, Kuebart, G, Lackovic, G, Ledbetter, JA, Lee, R, Llanes, D, Lunney, JK, McCullough, KC, Molitor, T, Nielsen, J, Niewold, TA, Pescovitz, MD, Perez de la Lastra, J, Rehakova, Z, Salmon, H, Schnitzlein, WM, Seebach, J, Simon, A, Sinkora, J, Sinkora, M, Stokes, CR, Summerfield, A, Sver, L, Thacker, E, Valpotic, I, Yang, H, Zuckermann, FA, and Zwart, R. Overview of the Third International Workshop on swine leukocyte differentiation antigens. Vet Immunol Immunopathol 80:5-23, 2001.

Goff WL, Johnson WC, Parish SM, Barrington GM, Elsasser TH, Davis WC, Valdez RA. IL-4 and IL-10 inhibition of IFN-g- and TNF-a-dependent nitric oxide production from bovine mononuclear phagocytes exposed to Babesia bovis merozoites. Vet Immunol Immunopath 84:237-251, 2002.

Valdez RA, McGuire TC, Brown WC, Davis WC, Jordan JM Knowles DP. Selective in vivo depletion of CD4+ T lymphocytes with anti-CD4 monoclonal antibody during acute infection of calves with Anaplasma marginale. Clin Diag Lab Immunol. 9:417-424, 2002.

Ahn JS, Konno A, Gebe JA, Aruffo A, Hamilton MJ, Park YH, Davis WC. Scavenger receptor cytsteine-rich domains 9 and 11 of WC1 are receptors for the WC1 counter receptor. J Leukoc Biol 72:382-390, 2002.

Ahn JS, Hamilton MJ, Davis WC, Park YH. Cloning of bovine CD69. Vet Immunol Immunopath 88:43-48, 2002.

Davis WC, Konzek RL, Haas K, Estes DM, Hamilton MJ, Call DR, Apostolopoulos V, McKenzie IFC. Use of the mannan receptor to selectively target vaccine antigens for processing and antigen presentation through the MHC class I and class II pathways. NY Acad Sci 969:119-125, 2002.

Goff WL, Johnson WC, Tuo W, Valdez RA, Parish SM, Barrington GM, Davis WC. The age-related innate immune response in calves to Babesia bovis involves IL-12 induction and IL-10 modulation. NY Acad Sci 969:164-168, 2002.

Lee S-U, Park Y-H, Davis WC, Hamilton MJ, Naessens J, Bohach GA. Molecular characterization of bovine CD26 upregulated by staphylococcal superantigen. Immunogenetics 54:216-220, 2002.

Herrmann LM, Cheevers WP, Wenbin T, Davis WC, Knowles DP, O’Rourke KI. CD21-positive follicular dendritic cells: A possible source of PrpSc in lymph node macrophages of scrapie-infected sheep. Am J Pathol 162:1075-1081, 2003.

Hines SA, Stone DM, Hines MT, Halperin DC, Knowles DP, Norton LK, Hamilton MJ, Davis WC, McGuire TC. Clearance of virulent, but not avirulent Rhodococcus equi from the lungs of adult horses is associated with intracytoplasmic IFN-g production by CD4+ and CD8+ T lymphocytes. Clin and Diag Lab Immunol. 10:208-215, 2003.

Barrington GM, Gay JM, Davis WC, Hamilton MJ, Evermann JF, Bradway DS. Temporal patterns of diagnostic results in serial samples from cattle with advanced paratuberculosis infections. J Vet Diagn Invest 15:195-200, 2003.

Lee S-U, Park Y-H, Davis WC, Fox LK, Bohach GA. The properties of human and bovine CD8+CD26+ T cells induced by a microbial superantigen. Adv Exp Biol 524:1-4, 2003.

Jasmer DP, Karanu F, Davis WC, McGuire TS. Abomasal lymph node responses to Haemonchus contortus intestinal antigens established in kid goats by infection or immunization with intestinal antigens. Parasit Immunol 25:59-68, 2003.

Waters WR, Miller JM, Palmer MV, Stabel JR, Jones DE, Koistinen KA, Steadham EM, Hamilton MJ, Davis WC, Bannantine JP. Experimental Mycobacterium avium subsp. Paratuberculosis infection of calves: early induction of a humoral and cellular immune response. Inf Immun 71:5130-5138, 2003.

David CW, Norrman J, Hammon HM, Davis WC, Blum JW. Cell proliferation, apoptosis, and B- and T-lymphocytes in Peyer’s Patches of the ileum, in thymus, and in lymph nodes of preterm calves and full-term calves at birth and on day 5 of life. J Dairy Sci 86:3321-3329, 2003.

Park YH, Joo YS, Park JY, Moon JS, Kim SH, Kwon NH, Ahn JS, Davis WC, Davies CJ. Characterization of lymphocyte subpopulations and major histocompatibility complex haplotypes of mastitis-resistant and susceptible cows. J Vet Sci 5:29-39, 2004.

Takahashi M, Tajima S, Okada K, Davis WC, Aida Y. Involvement of bovine leukemia virus Tax in induction and inhibition of apoptosis. Microbes and Infect. 6:584-595, 2004.

Koo HC, Park YH, Hamilton MJ, Barrington GM, Davies CJ, Kim JB, Dahl JL, Waters WR, Davis WC. Analysis of the immune response to M. avium supsp. Paratuberculosis in experimentally infected calves. Infect and Imm 72: 6870-6883, 2004.

Koo HC, Park YH, Hamilton MJ, Barrington GM, Davies CJ, Kim JB, Dahl JL, Waters WR, Davis WC. Analysis of the immune response to M. avium supsp. Paratuberculosis in experimentally infected calves. Infect and Imm 72: 6870-6883, 2004.

Koo HC, Park YH, Ahn J, Waters WR, Hamilton MJ, Barrington GM, Mosaad AA, Palmer MV, Sang S, Davis WC. Development of a latex bead agglutination assay for differential diagnosis of cattle infected with M. bovis and M. avium subsp paratuberculosis Clin and Diag Immunol 11: 1070-1074, 2004.

Tuo W, Davis WC, Fetterer R, Jenkins M, Boyd PC, Gasbarre LC, Dubey JP. Establishment of Neospora caninum antigen-specific T cell lines of primarily CD4+ T cells. Parasite Immunol 26:243-246, 2004.

Brown PA, Davis WC, Draghia-Akli R. Immune enhancing effects of growth hormone releasing hormone delivered by plasmid injection and electroporation. Molecular Therapy 10: 644-651, 2004.

Harbo SJ, Barrington GM, Allen AJ, Sample GL, Parish SM, Hamilton MJ, Davis WC. Characterization of lymphocyte populations by flow cytometry in a calf with sporadic juvenile lymphoma. Vet Clin Pathol 33:163-167, 2004.

Koo HC, Park YH, Ahn J, Waters WR, Palmer MV, Hamilton MJ, Barrington GM, Mosaad AA, Cho S-N, Shin SJ, Davis WC. Comparison of the enzyme linked immunosorbent, immunochromatographic, and latex bead agglutination assays for use in the serodiagnosis of bovine tuberculosis using rMB70 protein and ESAT-6 peptide as antigens. J Clin Microbiol 43:4498-4506, 2005.

Chang BS, Bohach GA, Lee S-U, Davis WC, Fox LK, Ferens WA, Seo KS, Koo HC, Kwon NH, Park YH. Immunosuppression by T regulatory cells in cows infected with staphylococcal superantigen. J Vet Sci 6:247-250, 2005.

G Maue AC, Davis WC, Palmer MV, Minion FC, Estes DM, Waters WR. Analysis of immune responses from M. bovis-infected cattle directed toward a recombinant ESAT-6:CFP10 fusion protein. Infect and Immun 73: 6659, 2005.

Davis WC, Hamilton MJ. Use of flow cytometry to characterize immunodeficiency syndromes in camelids. Small Rum Res 61:187-193, 2006.

Gulbahar MY, Davis WC, Yuksel H, Cabalar M. Immunohistochemical evaluation of inflammatory infiltrate in the skin ad lung of lambs naturally infected with sheeppox virus. Vet. Pathol 43:67-75, 2006.

Leong PP, Mohammad R, Ibrahim N, Ithnin N, Abdullah M, Davis WC, Seow HF. Phenotyping of lymphocytes expressing regulatory and effector markers in infiltrating ductal carcinoma of the breast. Immunol letters 102:229-236, 2006.

Saalmüller A, Lunney JK, Daubenberger C, Davis WC, Fischer U, Göbel TW, Griebel P, Hollemweguer E, Lasco T, Meister R, Schuberth H-J, Sestak K, Sopp P, Steinbach F, Xiao-Wei W, Aasted B. Summary of the animal homologue section of HLDA8. Cell Immunol 236:51-58, 2005.

Davis WC, Koo HC, Park YH, Hamilton MJ, Allen AJ, Barrington GM, Park KT, Kim JB, Dahl JL, Waters WR, Storset AK. Flow cytometric analysis of the immune response to M. avium subsp. paratuberculosis in experimentally infected calves. 8th International Colloquim on Paratuberculosis Proceedings (In press).