Regulatory T cells are critical for the maintenance of peripheral tolerance. There is currently limited evidence in support of the existence and role of Treg memory, as memory has primarily been studied in effector T cell populations. The primary challenge in identifying Treg memory lies in the fact that most Tregs are thought to be self-antigen-specific. Because most of these self-antigens are constitutively expressed, it is difficult to study memory populations that persist in the absence of cognate antigen. Mice infected with the neurotropic strain of the murine coronavirus, mouse hepatitis virus (MHV), develop acute encephalitis as well as immune-mediated acute and chronic demyelinating diseases. Tregs recognizing the immunodominant epitope of MHV have been identified and shown to suppress T cell responses during MHV infection. These virus-specific Tregs play a role in ameliorating immunopathology in MHV infection, as adoptive transfers of Tregs prior to infection increase survival and reduce demyelination. Because MHV infection represents a scenario in which Tregs of known antigen-specificity encounter non-persistent cognate antigen, this represents an ideal model to study the development of Treg memory. Through the use of transgenic mice expressing a TCR specific for the immunodominant epitope of MHV, preliminary experiments suggest that adoptively transferred Tregs form memory populations. My work aims to characterize these cells in terms of function and gene expression, as well as to assess the stability of Foxp3 expression by these cells.
Borbón TY, Scorza BM, Clay GM, Lima Nobre de Queiroz F, Sariol AJ, Bowen JL, Chen Y, Zhanbolat B, Parlet CP, Valadares DG, Cassel SL, Nauseef WM, Horswill AR, Sutterwala FS, Wilson ME. Coinfection with Leishmania major and Staphylococcus aureus enhances the pathologic responses to both microbes through a pathway involving IL-17A. PLoS Negl Trop Dis. 2019 May 20;13(5):e0007247. doi: 10.1371/journal.pntd.0007247. eCollection 2019 May. PubMed PMID: 31107882; PubMed Central PMCID: PMC6527190.
Wheeler DL, Sariol A, Meyerholz DK, Perlman S. Microglia are required for protection against lethal coronavirus encephalitis in mice. J Clin Invest. 2018 Mar 1;128(3):931-943. doi: 10.1172/JCI97229. Epub 2018 Jan 29. PubMed PMID:29376888; PubMed Central PMCID: PMC5824854.
Honors and Awards
- AAI Young Investigator Award for AIC, 2016
- Pharmacology T32 training grant, 2017, 2018