Flexibility accompanies commitment of memory CD4 lymphocytes derived from IL-4 locus-activated precursors.

Adeeku E, Gudapati P, Mendez-Fernandez Y, Van Kaer L, Boothby M
Proc Natl Acad Sci U S A. 2008 105 (27): 9307-12

PMID: 18591677 · PMCID: PMC2453725 · DOI:10.1073/pnas.0704807105

Differentiation of T helper (Th) subset 2 effector lymphocytes is thought to foreclose on IFN-gamma gene expression. Using an IL-4 locus modified to detect transcriptional induction of this effector cytokine gene in developing Th2 cells, we show here that these cells contributed effectively to a long-term memory population. A memory CD4 subset formed efficiently from an activated population after transcriptional induction of the IL-4 locus and differentiation into an IL-4-producing subset with Th2 characteristics. Memory lymphocytes derived from Th2 cells with IL-4 locus activation remained committed to transcriptional competence of Th2 cytokine genes when reactivated and cultured under strong Th1-polarizing conditions. This commitment to transcriptional competence at Th2 cytokine gene loci upon recall activation indicates that linear differentiation is a substantial component of type 2 memory. Strikingly, however, descendants of the Th2 population could turn on IFN-gamma expression when reactivated after a quiescent period, revealing an unexpected flexibility allowing activation of the forbidden IFN-gamma gene after reactivation and growth.

MeSH Terms (18)

Adoptive Transfer Alleles Animals CD4-Positive T-Lymphocytes Cell Differentiation Cell Lineage Cells, Cultured Gene Expression Regulation Green Fluorescent Proteins Immunologic Memory Interferon-gamma Interleukin-4 Lymphocyte Activation Mice Mice, Inbred BALB C Stem Cells T-Lymphocyte Subsets Th2 Cells

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