Mary Tompkins, DVM PhD
Director, NCSU Flow Cytometry and Cell Sorting Laboratory
Director, Veterinary Clinical Immunology Laboratory.
DVM: University of Illinois
PhD: University of Illinois
1996-present Professor, Department of Microbiology, Pathology and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC
1991-1996 Associate Professor, Department of Microbiology, Pathology and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC
1987-1991 Assistant Professor, Department of Microbiology, Pathology and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC
1986-1987 Clinical Assistant Professor, Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, IL
1984-1986 Visiting Assistant Professor, Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, IL
The research in this laboratory is directed towards understanding the immunopathogenesis of feline retrovirus infection. In particular, we are examining mechanisms of virus-induced immunosuppression and persistence, especially alterations in cytokine regulation and cell-mediated immunity.
For the past several years, my laboratory has been studying the immunopathogenesis of feline immunodeficiency virus (FIV), which is one of the best animal models for HIV infection. Our early studies described alterations in peripheral blood lymphocyte subset numbers, in vivo virus tropism, and disease progression. More recently we have described in detail cytokine dysregulation associated with FIV infection that leads to the inability of the infected cat to mount a successful cell mediated immune response to a secondary intracellular pathogen.
Currently we are looking at what appears to be aberrant expression of co-stimulatory molecules on the surface of T cells of FIV-infected cats and the role these molecules may play in the development of anergy and apoptosis leading to immune deficiency. We have found an increased expression of the co-stimulatory molecules B7.1, B7.2 and CTLA4 on T cells of FIV-infected cats. The B7 family of co-stimulatory molecules are normally found on professional antigen presenting cells, and interact with CD28 on T cells to provide the necessary second signal to T cells for proliferation, cytokine (IL2) secretion, and development of a T cell immune response. Several days after stimulation, CTLA4 is up-regulated on the activated T cells. Binding of CTLA4 by B7 molecules sends a negative signal, disengaging T cells from activation and further proliferation and inducing anergy. As T cell apoptosis and immunodeficiency is a characteristic of FIV-infected cats, we believe that B7-CTLA4 negative T cell signaling is favored in these cats. We developing in vitro cell culture models to study this signaling by transfecting cells with the B7 and CTLA4 molecules.
In collaboration with Dr. Wayne Tompkins (PHP Dept), we are also examining mechanisms by which CD8 cells in some FIV-infected cats are able to suppress virus replication. These CD8 cells are non-cytotoxic, non-MHC restricted suppressor cells. Using cell culture systems, we are looking at the effects of CD8 cells and/or CD8 cell soluble factors have on virus LTR function and regulation.
A third area of research, in collaboration with Dr. Lola Hudson (APR Dept) and Dr. Rick Meeker (UNC-CH), is the neuropathogenesis of FIV infection. This includes studies on the transport of virus across the BBB and the role of the CNS as a virus reservoir capable of re-seeding peripheral tissues with virus after termination of anti-retroviral therapy.
Methods used in the laboratory include cell and virus culture, flow cytometry, ELISAs, PCR, and competitive RT-PCR .
Dr. Wayne Tompkins (PHP), Dr. Lola Hudson (MBS), Dr. Rick Meeker (UNC-CH).
Tompkins MB, Bull ME, Dow JL, Ball J, Collisson EW, Winslow BJ, Vahlenkamp TW, Tompkins WAF. 2002. Feline Immunodeficiency Virus (FIV) Infection is Characterized by B7+CTLA4+ T Cell Apoptosis. J Infect Dis. 185: 1077-1093.
Ritchey JW, Levy JK, Bliss SK, Tompkins WAF, Tompkins MB. 2001 Constitutive expression of type 1 and type 2 cytokines by alveolar macrophages from feline immunodeficiency virus-infected cats. Vet Immunol Immunopathol. 79:83-100.
Butterworth JL, English RV, Jordan HL, Tompkins MB. 2001 Distribution of immune cells in the female reproductive tract in uninfected and FIV-infected cats. Vet Immunol Immunopathol. 83:37-51.
Liang YH, Hudson LC, Levy JK, Ritchey JW, Tompkins WAF, and Tompkins MB. 2000. T Cells Overexpressing Interferon-gamma and Interleukin-10 Are Found in Both the Thymus and Secondary Lymphoid Tissues of Feline Immunodeficiency Virus-Infected Cats. J Infect Dis. 181:564-57.
Gebhard DH, Dow J, Childers TA, Alvelo, JI, Tompkins MB, and Tompkins WAF. 1999. Progressive expansion of an L-selectin negative CD8 cell with anti-feline immunodeficiency virus (FIV) suppressor function in the circulation of FIV-infected cats. J Infect Dis. 180:1503-1513
Bragg, D.C., R.B. Meeker, B.A. Duff, R.V. English, and M.B. Tompkins. 1999. Neurotoxicity of FIV and FIV envelope protein in feline cortical cultures. Brain Res. 816:431-437.
Bucci, J., D. Gebhard, T. Childers, R. English, M. Tompkins, and W. Tompkins. 1998. The CD8+ phenotype mediating antiviral activity in FIV-infectged cats is characterized by reduced surface expression of the CD8 beta chain. J Inf Dis 178:968-977.
Levy, J., J. Ritchey, J. Rottman, M. Davidson, Y. Liang, H. Jordan, W. Tompkins, and M. Tompkins. 1998. Elevated interleukin-10-to-interleukin-12 ratio in feline immunodeficiency virus-infected cats predicts loss of type 1 immunity to Toxoplasma gondii. J Infect Dis 178:503.
Bucci,J. G., R. V. English, H. L. Jordan, T. A. Childers, M. B. Tompkins, and W. A. F. Tompkins. 1998. Mucosally transmitted feline immunodeficiency virus induces a CD8+ antiviral response that correlates with the reduction of cell-associated virus. J. Inf. Dis. 177:18-25.
Rottman, J. B., W. A. F. Tompkins, and M. B. Tompkins. 1996. A reverse transcription-quantitative competitive PCR (RT-PCR) technique to measure cytokine gene expression in domestic mammals. Vet Path. 33:242-248.
English, R. V., P. Nelson, C. M. Johnson, M. Nasisse, W. A. Tompkins, and M. B. Tompkins. 1994. Development of clinical disease in cats experimentally infected with feline immunodeficiency virus. J Infec Dis. 170:543.
Davidson, M. G., J. Rottman, R. V. English, M. R. Lappin, and M. B. Tompkins. 1993. Feline immunodeficiency virus predisposes cats to acute generalized toxoplasmosis. Am. J. Pathol. 143:1486.
English, R. V., C. M. Johnson, D. H. Gebhard, and M. B. Tompkins. 1993. In vivo lymphocyte tropism of feline immunodeficiency virus. J Virol. 67:5175.
Deb Anderson, Janet Dow, Linda English
Lab Contact Information:
Room B323, 513-6364
Room B324, 513-6363