Faculty Affairs: Faculty Interests Database
Christopher M. Snyder, PhD

Microbiology & Immunology
Mailing Address Contact Information
233 S. 10th Street, BLSB 526
Philadelphia, Pennsylvania 19107
United States
Phone: 215-503-2543
Christopher.Snyder@jefferson.edu
Expertise and Research Interests
Our lab is interested in understanding how T cells respond to chronic antigen stimulation during persistent viral infections, particularly cytomegalovirus (CMV) infections. CMV is a ubiquitous herpesvirus that infects most people world-wide and persists for life. In healthy individuals, CMV is continuously controlled by the immune system and causes little or no pathology, thanks largely to a potent and systemic T cell surveillance effort. In contrast, CMV is a major pathogen for immunocompromised individuals, causing severe morbidity and death. In addition, if CMV is transmitted to a developing fetus, the results can be devastating. In fact, CMV is a major congenital pathogen and a leading cause of birth defects in the developed world. For this reason, a vaccine that prevents CMV transmission would be enormously beneficial. CMV is a highly species specific pathogen and human CMV (HCMV) will not replicate in non-human cells. Therefore, to study the immune response to HCMV, we use murine CMV (MCMV), a homologue of HCMV and a natural mouse pathogen. Both viruses have evolved remarkably similar overall relationships with their hosts and thus MCMV is an excellent model to study HCMV immunobiology. Currently we focus on three broad areas of research:

1) We are investigating CMV-specific T cells in the salivary gland. This mucosal tissue serves as a major site of CMV release and transmission to new hosts. We are currently investigating the migration, localization, differentiation and function of CMV-specific T cells in this unique mucosal environment, as well as whether they can be effectively induced by vaccination.

2) The systemic surveillance of CMV-infected targets has profound effects on the responding T cell populations. Most notably, these cells increase in number over the life of the host. In fact, CMV-specific T cells are the largest known populations in the blood of healthy adults, comprising 4% to 5% of all T cells in circulation. A second overarching goal of our lab is to understand this remarkable accumulation of functional T cells, a process known as "memory inflation".

3) Because CMV stimulates such large numbers of T cells, we and others have proposed using it as a vaccine vector. Indeed, large numbers of T cells can be elicited by recombinant antigens encoded in the CMV genome and we have shown that a non-pathogenic, spread-defective version of MCMV can sustain large numbers of T cells. Therefore, a third goal of our lab is to investigate CMV-based vaccines that stimulate tumor-specific immunity.
Keywords
T cells; CD8; cytomegalovirus; CMV; MCMV; murine cytomegalovirus; immune memory; chronic infection; immunology; microbiology; herpesvirus
Publications
  • Farrington LA, Smith TA, Grey F, Hill AB, Snyder CM. Competition for antigen at the level of the APC is a major determinant of immunodominance during memory inflation in murine cytomegalovirus infection. J Immunol. Apr 1;190(7):3410-6 (2013). link to article
  • Turula H, Smith CJ, Grey F, Zurbach KA, Snyder CM. Competition between T cells maintains clonal dominance during memory inflation induced by MCMV. Eur J Immunol. Apr;43(5):1252-63. (2013) link to article
  • Snyder CM. Editorial: Once more unto the breach, dear friends: CMV reactivates when the walls come down. J Leukoc Biol. Nov;92(5):915-8. (2012) link to article
  • Snyder CM. Buffered Memory: A hypothesis for the maintenance of functional, virus-specific CD8+ T cells during cytomegalovirus infection. Immunol. Res. EPub Nov. 6, (2011) link to article
  • Snyder CM, Cho KS, Bonnett EL, Allan JA, Hill AB. Sustained CD8+ T Cell Memory Inflation after Infection with a Single-Cycle Cytomegalovirus. PLoS Pathogens. 7(10): e1002295 (2011). link to article
  • Heiser RA, Snyder CM, Wysocki LJ. Aborted Germinal Center Reactions and B Cell Memory by Follicular T Cells Specific for a BCR V Region Peptide J Immunol. 187 (1): 212-21 (2011). link to article
  • Snyder CM, Allan JA, Bonnett EL, Doom CM, Hill AB. Cross-presentation of a replication deficient virus is sufficient to prime the majority of MCMV-specific CD8+ T cells PLoS One 5 (3): e9681 (2010). link to article
  • Snyder CM, Lowendorf A, Bonnett EL, Croft M, Benedict CA, Hill AB. CD4+ T cell help has an epitope-dependent impact on CD8+ T cell memory inflation during MCMV infection J Immunol. 183 (6): 3932-41 (2009). link to article
  • Snyder CM, Cho KS, Bonnett EL, van Dommelen S, Shellam GR, Hill AB. "Memory Inflation During Chronic Viral Infection is Maintained by Continuous Production of Short-Lived Effectors" Immunity 29:650-59 (2008). link to article
  • Snyder CM, Mardones G, Ladinsky MS, Howell KE. "GMx33 associates with the trans-Golgi matrix in a dynamic manner and sorts within tubules exiting the Golgi." Mol Biol Cell.17:511-24 (2006). link to article
  • Mardones G, Snyder CM, Howell KE. "cis-Golgi Matrix Proteins Move Directly to ER Exit Sites by association with Tubules" Mol Biol Cell. 17:525-38 (2006). link to article
  • Snyder CM, Aviszus K, Heiser RA, Tonkin DR, Guth AM, Wysocki LJ. "Activation and tolerance in CD4(+) T cells reactive to an immunoglobulin variable region." J Exp Med. 200:1-11 (2004). link to article
  • Snyder CM, Zhang X, Wysocki LJ. "Negligible class II MHC presentation of B cell receptor-derived peptides by high density resting B cells." J Immunol. 168:3865-73 (2002). link to article

Last Updated by Christopher Snyder, PhD: Thursday, January 5, 2012 11:25:12 AM

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