Jason M. Schenkel
Entering Class: 2009
Human Communications Sciences and Molecular Biology majors
University of Minnesota
Microbiology, Immunology and Cancer Biology Graduate Program
Honors and Awards:
- University of Minnesota Foundation Beatrice Z. Milne and Theodore Brandenburg Award, 2014
- Ruth L. Kirschstein National Research Service Award for Predoctoral MD/PhD Fellows, National Institute of Diabetes and Digestive and Kidney Diseases, 2013-2016
MSTP Student Governance:
- Student Advisory Committee 2013-15
- Student Admissions Committe, 2013
Thesis Advisor: David Masopust, Ph.D.
Dynamics and functionality of CD8 T cell immunity within the female reproductive tract
The female reproductive tract (FRT) is a heterogenous mucosal tissue that is exposed to commensal flora, undergoes periodic remodeling, and supports fertilization, yet serves as a major site of microbial infection. Due to its unique physiology and vulnerability to microbes, it is important to have a better understanding of the dynamics of the adaptive immune response within the FRT. Using flow cytometric analyses paired with immunofluorescence microscopy we are characterizing the kinetics, localization (anatomically and subanatomically), phenotype and function of antigen specific CD8 T cells present in the FRT during a systemic infection. So far, we have found that effector CD8 T cells migrated into the vagina, cervix, uterine horns and ovaries, where they localized within the lamina propria, epithelium, or unexpectedly, in large lymphoid aggregates where they were associated with CD11c/MHCII+ cells. After pathogen clearance, maintenance of memory CD8 T cells varies greatly based on location within the FRT. The cellularity and number of these lymphoid aggregates changes dramatically throughout the response. We are now exploiting local challenge models to visualize the role of these structures in CD8 T cell migration, antigen trafficking and presentation, and supporting in situ recall responses. These studies should be highly relevant for understanding protective cell-mediated immunity within the female genital mucosa.
Hondowicz BD, An D, Schenkel JM, Kim KS, Steach HR, Krishnamurty AT, Keitany GJ, Garza EN, Fraser KA, Moon JJ, Altemeier WA, Masopust D, Pepper M. Interleukin-2-Dependent Allergen-Specific Tissue-Resident Memory Cells Drive Asthma. Immunity. 2016 Jan 19;44(1):155-66.
Kohlhapp FJ, Broucek JR, Hughes T, Huelsmann EJ, Lusciks J, Zayas JP, Dolubizno H, Fleetwood VA, Grin A, Hill GE, Poshepny JL, Nabatiyan A, Ruby CE, Snook JD, Rudra JS, Schenkel JM, Masopust D, Zloza A, Kaufman HL. NK cells and CD8+ T cells cooperate to improve therapeutic responses in melanoma treated with interleukin-2 (IL-2) and CTLA-4 blockade. J Immunother Cancer. 2015 May 19;3:18. PMCID: PMC4437746
Steinert EM, Schenkel JM, Fraser KA, Beura LK, Manlove LS, Igyártó BZ, Southern PJ, Masopust D. Quantifying Memory CD8 T Cells Reveals Regionalization of Immunosurveillance. Cell. 2015 May 7;161(4):737-49.
Pauken KE, Nelson CE, Martinov T, Spanier JA, Heffernan JR, Sahli NL, Quarnstrom CF, Osum KC, Schenkel JM, Jenkins MK, Blazar BR, Vezys V, Fife BT. Cutting edge: identification of autoreactive CD4+ and CD8+ T cell subsets resistant to PD-1 pathway blockade. J Immunol. 2015 Apr 15;194(8):3551-5.
Schenkel JM, Masopust D. Tissue-resident memory T cells. Immunity. 2014 Dec 18;41(6):886-97. PMCID: PMC4276131
Beura LK, Anderson KG, Schenkel JM, Locquiao JJ, Fraser KA, Vezys V, Pepper M, Masopust D. Lymphocytic choriomeningitis virus persistence promotes effector-like memory differentiation and enhances mucosal T cell distribution. J Leukoc Biol. 2015 Feb;97(2):217-25. PMCID: PMC4304422
Schenkel JM, Fraser KA, Beura LK, Pauken KE, Vezys V, Masopust D. T cell memory. Resident memory CD8 T cells trigger protective innate and adaptive immune responses. Science. 2014 Oct 3;346(6205):98-101. PMCID: PMC4449618
Mahmud SA, Manlove LS, Schmitz HM, Xing Y, Wang Y, Owen DL, Schenkel JM, Boomer JS, Green JM, Yagita H, Chi H, Hogquist KA, Farrar MA. Costimulation via the tumor-necrosis factor receptor superfamily couples TCR signal strength to the thymic differentiation of regulatory T cells. Nat Immunol. 2014 May;15(5):473-81. PMCID: PMC4000541
Schenkel JM*, Fraser KA, Masopust D. Cutting edge: resident memory CD8 T cells occupy frontline niches in secondary lymphoid organs. J Immunol. 2014 Apr 1;192(7):2961-4. PMCID: PMC3965619 *co-first author
Sakai S, Kauffman KD, Schenkel JM, McBerry CC, Mayer-Barber KD, Masopust D, Barber DL. Cutting edge: control of Mycobacterium tuberculosis infection by a subset of lung parenchyma-homing CD4 T cells. J Immunol. 2014 Apr 1;192(7):2965-9. PMCID: PMC4010124
Schenkel JM, Masopust D. Identification of a resident T-cell memory core transcriptional signature. Immunol Cell Biol. 2014 Jan;92(1):8-9.
Fraser KA, Schenkel JM, Jameson SC, Vezys V, Masopust D. Preexisting high frequencies of memory CD8+ T cells favor rapid memory differentiation and preservation of proliferative potential upon boosting. Immunity. 2013 Jul 25;39(1):171-83. PMCID: PMC3979587
Masopust D, Schenkel JM. The integration of T cell migration, differentiation and function. Nat Rev Immunol. 2013 May;13(5):309-20. doi: 10.1038/nri3442. Review.
Schenkel JM, Fraser KA, Vezys V, Masopust D. Sensing and alarm function of resident memory CD8+ T cells. Nat Immunol. 2013 May;14(5):509-13. PMCID: PMC3631432
Casey KA, Fraser KA, Schenkel JM, Moran A, Abt MC, Beura LK, Lucas PJ, Artis D, Wherry EJ, Hogquist K, Vezys V, Masopust D. Antigen-independent differentiation and maintenance of effector-like resident memory T cells in tissues. J Immunol. 2012 May 15;188(10):4866-75. PMCID: PMC3345065
Hamilton SE, Schenkel JM, Akue AD, Jameson SC. IL-2 complex treatment can protect naive mice from bacterial and viral infection. J Immunol. 2010 Dec 1;185(11):6584-90. PMCID: PMC3016939
Zloza A, Kohlhapp FJ, Lyons GE, Schenkel JM, Moore TV, Lacek AT, O'Sullivan JA, Varanasi V, Williams JW, Jagoda MC, Bellavance EC, Marzo AL, Thomas PG, Zafirova B, Polić B, Al-Harthi L, Sperling AI, Guevara-Patiño JA. NKG2D signaling on CD8⁺ T cells represses T-bet and rescues CD4-unhelped CD8⁺ T cell memory recall but not effector responses. Nat Med. 2012 Feb 26;18(3):422-8.
Schenkel JM, Zloza A, Li W, Narasipura SD, Al-Harthi L. Beta-catenin signaling mediates CD4 expression on mature CD8+ T cells. J Immunol. 2010 Aug 15;185(4):2013-9. Epub 2010 Jul 14.
Zloza A, Schenkel JM, Tenorio AR, Martinson JA, Jeziorczak PM, Al-Harthi L. Potent HIV-specific responses are enriched in a unique subset of CD8+ T cells that coexpresses CD4 on its surface. Blood. 2009 Oct 29;114(18):3841-53.