Stephen C Jameson
University of Minnesota, MN·Microbiology & Immunology
The immune system has to walk a tightrope: respond hard enough to clear infections and cancers, but not so hard that it attacks the body's own tissues or causes collateral damage. T cells sit at the center of that balance.
- Fields
Microbiology & Immunology
Genetics
Medicine & Clinical Research
- Topics
CD8+ T cells
immunological tolerance
autoimmunity
- Grants
- 5 known grants, through Jun 2030
What they work on
- Build mouse model systems to define the development, maintenance and antigen specificity of Helios+ CD8+ T cells, a memory-phenotype population proposed to restrain excessive and self-directed immune responses.
- Use single-cell RNA and ATAC sequencing in new single-chain T cell receptor transgenic mice to define the gene regulation that silences self-reactive CD8+ T cells recognizing the melanocyte protein Trp2 without deleting them.
- Classify self-reactive T cell clones into imperfectly deleted, anergized, non-anergized and tolerance-evading types using deep sequencing of the TCR-alpha repertoire and retrogenic mouse models.
- Determine which forms of CD8+ tolerance leave mice most vulnerable to autoimmunity, using an established model of vaccination-induced vitiligo provoked by inflammation.
- Test how introducing versus destroying senescent cells changes the numbers and function of naive and memory T and B cells during defined viral infections in mouse models.
- Determine whether NK cells and other immune populations normally kill senescent cells, and whether this culling feedback loop fails with age.
- Use CRISPR/Cas9 to delete receptors for SASP inflammatory factors in mouse and human T cells and test whether these factors alone impose age-related inhibitory changes.
- Eliminate T cell responsiveness to the cytokines IL-7 and IL-15 after memory has already formed, using inducible gene knockouts, to test their role in steady-state memory maintenance and during bystander infections.
- Test whether the transcription factor KLF2 and its target S1PR1, a cell-exit receptor, set the identity of recirculating versus tissue-resident memory T cells, using inducible genetic models and statin treatment.
More about the research
Work in this lab centers on CD8+ T cells—the killer cells that destroy infected or abnormal cells—and asks how these cells are held in check against self, how their memory of past infections lasts for years, and how aging erodes both. The projects range from identifying an unusual regulatory CD8+ T cell population, to mapping how tolerance to self is enforced without killing the offending cells, to testing whether worn-out "senescent" cells elsewhere in the body sabotage immune responses.
Why it matters
Autoimmune diseases arise when tolerance to self fails, and defining how CD8+ killer T cells are silenced rather than deleted could point to where that safeguard breaks, with vitiligo as a concrete model. Understanding why older people fight infections poorly, and whether drugs that clear senescent cells restore immune control, could inform strategies for the elderly, who were strikingly vulnerable during COVID-19. Clarifying what maintains memory T cells may guide ways to strengthen vaccine-induced protection or to reshape T cell responses for cancer immunotherapy or to damp harmful ones.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jenna Bartley
University of Connecticut, CT·Microbiology & Immunology
Test whether clearing senescent cells with senolytic drugs before vaccination improves cell-mediated and antibody responses to recombinant flu nucleoprotein and adjuvanted inactivated flu vaccines in aged mice.
Yanjiao Zhou
University of Connecticut, CT·Microbiology & Immunology
Test whether senescent cells reshape the gut microbiome and its metabolites by transplanting or genetically clearing senescent cells in older male and female mice, using the p21-Cre mouse model.
Peter Aidan Savage
University of Chicago, IL·Microbiology & Immunology
Define the biophysical and structural basis by which T cell receptors from regulatory and conventional CD4+ T cells recognize the same self-peptide displayed on MHC class II, testing whether a more centered binding mode increases signaling sensitivity.
The school
University of Minnesota: 88 labs on PI Pages, $1.4B a year on research, 722 research doctorates a year.
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