Functionally distinct subsets of CD4 helper T cells, including T follicular helper (Tfh) and T helper type 1 (Th1) subsets, critically govern protective immunity via the induction and maturation of humoral immune responses and phagocyte activation, respectively. Proper genetic programming is required for CD4 T cell helper differentiation, function, and memory formation and dysregulated and inefficient CD4 T cell responses have been linked to suboptimal immunity against multiple acute and chronic infections. Current genetic approaches to interrogate CD4 T cell biology have been largely focused on defining transcriptional programming networks, but transcription factor function and gene expression ultimately depend on epigenetic programming, which represents a major knowledge gap in our understanding of CD4 T cell biology. Thus, fundamental questions remain to be addressed regarding the epigenetic genetic mechanisms that determine pathogen-specific effector and memory CD4 T cell differentiation and function. 

Ten-eleven-translocation (TET) family proteins demethylate DNA via a step-wise oxidation of 5’ methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Presence of 5hmC correlates with accessible chromatin. Three TET family proteins (TET1, 2 and 3) act either individually or together to regulate gene expression changes in developing thymocytes, B cells and memory CD8 T cells. However, how or whether these enzymes regulate the differentiation and function of effector and memory CD4 T cells has not been investigated.

The central hypothesis for my dissertation studies is that mature, peripheral CD4 T cell differentiation and function is governed by activity of TET proteins.

Publications

Johnson JT, Surette FA, Ausdal GR, Shah M, Minns AM, Lindner SE, Zander RA, Butler NS. CD4 T Cell-Derived IL-21 Is Critical for Sustaining Plasmodium Infection-Induced Germinal Center Responses and Promoting the Selection of Memory B Cells with Recall Potential. J Immunol. 2024 May 1;212(9):1467-1478. doi: 10.4049/jimmunol.2300683. PMID: 38477614; PMCID: PMC11018477.

Vijay R., Guthmiller J.J., Sturtz A.J., Crooks S., Johnson J.T… Butler N.S. Hemolysis-associated phosphatidylserine exposure promotes polyclonal plasmablast differentiation. J Exp Med. 2021 Jun 7;218(6):e20202359. doi: 10.1084/jem.20202359.

Honors & Awards

• NIAID F31 Predoctoral Fellowship – AI164640
• Trainee Abstract Award – AAI Immunology2021 May 2021
• NIAID T32 Predoctoral Training Grant – AI007511 2019-2021