Memory phenotype CD4 t cells undergoing rapid, nonburst-like, cytokine-driven proliferation can be distinguished from antigen-experienced memory cells

Marrack, Philippa, Younes, Souheil-Antoine, Punkosdy, George, Caucheteux, Stephane, Chen, Tao, Grossman, Zvi and Paul, William E. 2011. Memory phenotype CD4 t cells undergoing rapid, nonburst-like, cytokine-driven proliferation can be distinguished from antigen-experienced memory cells. PLoS Biology 9 (10) , e1001171. 10.1371/journal.pbio.1001171

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Abstract

Memory phenotype (CD44bright, CD25negative) CD4 spleen and lymph node T cells (MP cells) proliferate rapidly in normal or germ-free donors, with BrdU uptake rates of 6% to 10% per day and Ki-67 positivity of 18% to 35%. The rapid proliferation of MP cells stands in contrast to the much slower proliferation of lymphocytic choriomeningitis virus (LCMV)-specific memory cells that divide at rates ranging from <1% to 2% per day over the period from 15 to 60 days after LCMV infection. Anti-MHC class II antibodies fail to inhibit the in situ proliferation of MP cells, implying a non–T-cell receptor (TCR)-driven proliferation. Such proliferation is partially inhibited by anti–IL-7Rα antibody. The sequence diversity of TCRβ CDR3 gene segments is comparable among the proliferating and quiescent MP cells from conventional and germ-free mice, implying that the majority of proliferating MP cells have not recently derived from a small cohort of cells that expand through multiple continuous rounds of cell division. We propose that MP cells constitute a diverse cell population, containing a subpopulation of slowly dividing authentic antigen-primed memory cells and a majority population of rapidly proliferating cells that did not arise from naïve cells through conventional antigen-driven clonal expansion.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	Public Library of Science
ISSN:	1545-7885
Date of First Compliant Deposit:	30 March 2016
Last Modified:	10 May 2023 12:47
URI:	https://orca.cardiff.ac.uk/id/eprint/52737

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