Associate ProfessorOffice: Charles H. Clapp Building, Room 216
I maintain an open door policy and don't limit my availability to students. I am available to meet and discuss the class with students pretty much anytime. Please stop by my office or lab whenever it is convenient for you. If I am not available at that particular time, we will make an appointment to meet within 2-3 days. To make sure I will be there and available to talk with you, you can email or call to set up an appointment.
Associate Professor of Immunobiology
Scientific Director, Molecular Histology and Fluorescence Imaging Core Facility
Scientific Director, EMTrix (UM Electron Microscopy Core Facility)
BIOB 410 - Immunology
BIOB 411 - Immunology Lab
BIOM 502 - Advanced Immunology
BIOB 596 - Principles of Light Microscopy
B.A. University of La Verne, La Verne, CA., 1987
M.S. California State Polytechnic University, Pomona, 1992
Ph.D. Oregon Health & Science University, Portland, OR, 2001
Work in my lab focuses on CD4+ T lymphocyte activation and effector subset differentiation.
- The biological consequences for individual T cells of signaling induced by APC-derived membrane molecules after their transfer to T cells at the T-APC immunological synapse, a process termed “trogocytosis”;
- The impact of the herbicide Atrazine on the activation of CD4+ T cells and the mechanism underlying a significant increase in Foxp3+ regulatory T cells
The Role of Trogocytosis in CD4 Effector Subset and Memory T Cell DIfferentiation
CD4+ T lymphocytes recognize antigenic peptide fragments presented on the surface of antigen presenting cells (APC) by major histocompatiblility complex (MHC) class II proteins. This initial antigen recognition is followed by large-scale spatial and temporal molecular rearrangements of plasma membrane proteins and intracellular signaling molecule leading to the formation of an ordered structure at the T-APC interface termed the immunological synapse. The synapse is involved in T cell signaling as well as the site for delivery of T cell effector functions. Our lab has previously shown that that molecules from the APC are transferred to the T cell at the immune synapse in a process called trogocytosis.
We are examining the biological significance of intercellular transfer of molecules from APC to T cells. We've shown that APC-derived molecules continue to engage their receptors on T cell and sustain intracellular sigaling within the T cell. This signaling leads to the selective survival of these T cells in culture and drives the production of some effector cytokines (e.g. IL-4, IL-6, IL-21), while inhibiting production of other cytokines (e.g. IFN-gamma). Our work suggests that trogocytosis-mediated signaling ultimately induces expression of transcription factors and effector cytokines within the cells consistent with differentiation of cells towards a TH2 phenotype. the trogocytosis-mediated signaling also can induce the conversion of polarized TH1 cells toward a TH2 phenotype. We hypothesize that this may play an important role in control of immune responses - promoting TH2 and limiting potentially damaging TH1 responses.
In addition to driving TH2-associated gene expression patterns, we have also observed that trogycytosis-ediated signaling induces a cellular phenotype consistent with a second CD4 effector subset, the Bcl-6+IL-21+CXCR5+ follicular T helper cells (TFH). Our current work involves examining the potential for trogocytosis-mediated signaling to induce CD4 differentiation to a TFH phentype and to analyze its impact on antibody responses in vivo.
Finally, we are just beginning experiments to analyze whether trogocytosis and trogocytosis-associated signaling have a role in asymmetrical division and the development of memory T cells from naive precursors.
Immunotoxicology of Atrazine
We are examining the impact on Atrazine on the activation and differentiation of CD4+ T cells. Atrazine is a very widely applied herbicide that the USGS estimates contaminates 70% of the ground water in the US. It has been linked to birth defects, cancer, immune developmental defects and modulation of immune cell effector functions. We have shown that Atrazine inhibits CD4+ T lymphocyte proliferation and effector function. In addition, we have shown that the frequency of Foxp3 positive regulatory T cells (Treg) doubles in atrazine-treated cultures. This is largely due to elevated levels of cAMP, as Atrazine is a potent phosphidiesterase inhibitor. We have recently found that male and female T cells repsond differently to atrazine exposure. Atrazine's other biochemical effect is to induce expression of aromatase, which converts androgens to estrogen. We are currently examining the impact of Atrazine-induced elevated estrogen on the induction of Tregs and Atrazine-associated inhibition of T cell activation.
We are also examining whether the effects of atrazine on T cell function and fate are directly on the T cell or whether it is working via altering antigen presenting cell phenotype/activity.
Our ultimate goal with this project is to examine whether in vivo atrazine exposure alters or limits an in vivo immune response to tumors or infectious disease.
Field of Study
Reed, S.J. and Wetzel, S.A. (2019) Trogocytosis-Mediated Intracellular Signaling in CD4+ T Cells Drives TH2-Associated Effector Cytokine Production and Differentiation. The Journal of Immunology. (In Press)
Jim Reed and Scott Wetzel. (2018) “CD4+T cell Differentiation and Activation” in Immunotoxicity Testing: Methods and Protocols. Rockwell, DeWitt and Bowman editors. Springer Publishing. 1083:335-351. PMID:29882148
Thueson, L.E; Emmons, .E., Browning, D.B., Kreitinger, J.M.; Sheherd, D.M.; Wetzel S.A. (2015). In vitro Exposure To The Herbicide Atrazine Inhibits T Cell Activation, Proliferation, and Cytokine Production and Significantly Increases The Frequency Of Foxp3+ Regulatory T Cells. Toxicological Sciences. 143:418-29. PMID: 25433234
Osborne, D.G. and Wetzel, S.A. (2012) Trogocytosis leads to sustained signaling in CD4+ T cells. The Journal of Immunology, 189(10):4728-39. PMID: 23066151
Doherty, M., Osborne, D.G., Browning, D.B., Parker, D.C. Wetzel, S.A. (2010) Anergic CD4+ T cells form mature immunological synapses with enhanced accumulation of c-Cbl and Cbl-b. The Journal of Immunology, 184:3598-3608. PMCID: PMC2843782
Thauland, T.J.; Y. Koguchi, R.Varma, S.A. Wetzel, M.L. Dustin, and D.C. Parker. (2008). TH1 and TH2 cells fom morphologically distinct immunological synapses . The Journal of Immunology, 181:393-9
Blake, D.J.; Wetzel, S.A.; Jean C Pfau, J.C. (2008) Autoantibodies from mice exposed to Libby amphibole asbestos bind SSA/Ro52-enriched apoptotic blebs of murine macrophages. Toxicology, 246:172-9
Scott A. Wetzel and D.C. Parker. (2006) MHC transfer from APC to T cells following antigen recognition. Critical Reviews in Immunology. 26:1-21
Tara J. Dillon, K.D.Carey, S.A. Wetzel, D.C. Parker, P.J.S. Stork. (2005). Regulation of the Small GTPase Rap1 and Extracellular Signal-Regulated Kinases by the Costimulatory Molecule CTLA-4. Molecular Cell Biology, 25(10):4117-4128
Scott A. Wetzel, T. W. McKeithan, D.C. Parker. (2005). Peptide-specific intercellular transfer of MHC class II to CD4+ T cells directly from the immunological synapse upon cellular dissociation. The Journal of Immunology. 174(1): 80-9
Tara J. Dillon, Vladimir Karpitski, Scott A. Wetzel, David C. Parker, Andrey S. Shaw, and Philip J. S. Stork (2003). Ectopic B-Raf expression enhances extracellular signal-regulated kinase (ERK) Signaling in T cells and prevents antigen presenting cell-induced anergy. Journal of Biological Chemistry, 278:35940.
Wetzel, S.A. ; McKeithan, T.W.; Parker D.C. (2002) Live Cell Dynamics and the Role of Costimulation in Immunological Synapse Formation. The Journal of Immunology. 169(11):6092
Sperry P.J.; Cua D.J.; Wetzel S.A.; Adler-Moore, J.A. (1998) Antimicrobial activity of AmBisome and non-liposomal Amphotericin B following uptake of Candida glabrata by murine epidermal Langerhans cells. Medical Mycology 36(3):135 - 141
Primus, F.J.; Finch, M.D.; Wetzel, S.A.; Masci, A.M.; Schlom, J.; Kashmiri, S.V.S. (1994) Monoclonal Antibody Gene Transfer: Implications for Tumor - Specific Cell - Mediated Cytotoxicity. Annals of the New York Academy of Science. 716:154 - 166
Specialized Research Interests
Trogocytosis, T cell signaling and Immunological synapse biology.
1996 - 2004 Instructor, Medical School Immunology, Oregon Health & Science University, Portland, OR
1997 - 2004 Instructor, Clinical Laboratory Science Program, Oregon Health & Science University, Portland, OR
2002 – 2004 Instructor, Biotechnology Department, Portland Community College, Portland, OR
2002 – 2011 Faculty Member, International Course on 3D Microscopy of Living Cells, University of British Columbia, Vancouver, BC, Canada
2005 - 2013 Assistant Professor, Division of Biological Sciences and Center for Environmental Health Sciences, University of Montana, Missoula, MT
2013 - Present Associate Professor, Division of Biological Sciences and Center for Environmental Health Sciences, University of Montana, Missoula, MT
American Association of Immunologists
University of Montana Center for Environmental Health Sciences
UM Interdepartmental Immunology Graduate Degree Track
UM DBS Cellular, Molecular, Microbial Biology Graduate Program
UM Molecular Bioscience Gratuate Program