LYMPHOCYTE-MEDIATED IMMUNITY TO ANAPLASMA MARGINALE

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DESCRIPTION: Candidate: Reginald A. Valdez obtained his D.V.M. from Colorado State University in 1990. Following a year in private practice, he obtained a 3-year fellowship in Clinical Parasitology supported by the Merck Foundation and obtained a M.S. in Veterinary Parasitology in 1994 from the University of Illinois. During this period he also completed a 3-year clinical residency in large animal internal medicine. He then entered the post-D.V.M. Comparative Pathology Residency training program in the Department of Veterinary Microbiology and Pathology at Washington State University. The candidate has completed the 2-year didactic work in diagnostic veterinary pathology and basic biomedical sciences expected of Ph.D. candidates in the Department and is now ready to undertake the dissertation research described in this proposal. There was some uncertainty as to the extent of the problem of acute anaplasmosis infection in cattle and how the research findings might impact the field. Since Dr. Valdez is lacking in original bench research experience, the application would have been strengthened by the presence of some preliminary data generated by the candidate. The application is scored in the excellent range. Mentor: Donald P. Knowles is the mentor. He is an Associate Professor in the Department of Veterinary Microbiology and Pathology. Dr. Knowles obtained his D.V.M. in 1982 from the University of Illinois and his Ph.D. from Washington State University in 1988. He is a research leader in the Animal Disease Research Unit, ARS/USDA. Dr. Knowles has funding from the Office of International Cooperative Development until September 1997. He is also a coinvestigator on Dr. W.P. Cheevers' NIH grant which is funded until September 1998 and an Arthritis Foundation grant until June 1997. Dr. Knowles listed 14 selected refereed publications since 1993 and is very productive. Dr. Knowles has been a member of the graduate faculty since 1991, and has served as the major advisor for one M.S. and two Ph.D. graduate students and for three post-doctoral scientists. Career Development Plan: Dr. Valdez will attend weekly research seminars. In addition, Dr. Valdez will continue to participate in the Advances in Immunology seminar series which are presented by outside speakers. Dr. Valdez's advisory committee includes Drs. Knowles (sponsor), Traves C. McGuire (a professor who has considerable experience in lentivirus immune mechanism), William C. Davis (a professor who has interests in immunity to lentiviruses and hemoparasites and developed the specific anti-lymphocyte monoclonal antibodies described in Dr.Valdez's proposal) and Wendy Brown (a recent addition to the Department who has experience in defining the role of bovine T-lymphocytes in hemoprotozoan infections). Although Dr. Terry McElwain s C.V. was not included, he is the Director of the Washington Animal Disease Diagnostic Laboratory, has a long-term research record defining the pathogenesis and immunity of infection with bovine babesiosis, bovine anaplasmosis and bovine leukemia virus infection, and is also a committee member. Research Plan: The overall goal of this proposal is to identify lymphocyte-mediated effector mechanisms involved in the development of protective immunity in cattle infected with A. marginale. The experimental approach involves inoculation of calves with A. marginale, mouse monoclonal antibodies against CD4+, gd T cells, and IFN-g, and observation of clinical signs and evaluation of hematologic parameters. Flow cytometric analysis of CD4+, CD8+, and gd-T cells, splenocyte IFN-g production assay, and isotype specific antibody titration are 3 major assays to be performed. Results will be statistically analyzed. Environment & Institutional Commitment: The training environment at Washington State includes post-B.S. predoctoral students, post-Ph.D. students, and Ph.D. research training for clinically trained veterinarians. Training programs include the Immunology Training Program (sponsored by NIH-NIAID for post-Ph.D. and post-DVM training), Pathobiology Training Program (sponsored by NIH-NIAID for post-DVM training), Biotechnology Training Program (USDA-sponsored for Ph.D. training) and individual fellowships (NIH, NRSA, PSA, MCSDA, CIA, Rockefeller Foundation, and USAID Biotechnology). These programs are multidisciplinary in nature and provide a basic science training environment. The total number of trainees include 11 M.S. students, 85 Ph.D. students and 34 post-Ph.D. fellows. Dr. Valdez will have access to all facilities assigned to the sponsor and centralized facilities such as the Animal Disease Research Unit, ARS/USDA. Although the candidate wrote "see attached continuation page for a list of major equipment," this page could not be found. Cell culture and flow cytometry facilities which are essential for the proposed study were not described. These equipment and facilities are, however, assumed to be available in the laboratory of Dr. Knowles based on his research activities.