Precursor central memory versus effector cell fate and naïve CD4+ T cell heterogeneity.

Publication Type	Academic Article
Authors	Deep D, Gudjonson H, Brown C, Rose S, Sharma R, Paucar Iza Y, Hong S, Hemmers S, Schizas M, Wang Z, Chen Y, Wesemann D, Pascual V, Pe'er D, Rudensky A
Journal	J Exp Med
Volume	221
Issue	10
Date Published	09/25/2024
ISSN	1540-9538
Keywords	CD4-Positive T-Lymphocytes, Cell Differentiation, Immunologic Memory, Memory T Cells
Abstract	Upon antigenic stimulation, naïve CD4+ T cells can give rise to phenotypically distinct effector T helper cells and long-lived memory T cells. We computationally reconstructed the in vivo trajectory of CD4+ T cell differentiation during a type I inflammatory immune response and identified two distinct differentiation paths for effector and precursor central memory T cells arising directly from naïve CD4+ T cells. Unexpectedly, our studies revealed heterogeneity among naïve CD4+ T cells, which are typically considered homogeneous save for their diverse T cell receptor usage. Specifically, a previously unappreciated population of naïve CD4+ T cells sensing environmental type I IFN exhibited distinct activation thresholds, suggesting that naïve CD4+ T cell differentiation potential may be influenced by environmental cues. This population was expanded in human viral infection and type I IFN response-lined autoimmunity. Understanding the relevance of naïve T cell heterogeneity to beneficial and maladaptive T cell responses may have therapeutic implications for adoptive T cell therapies in cancer immunotherapy and vaccination.
DOI	10.1084/jem.20231193
PubMed ID	39321257
PubMed Central ID	PMC11448869