Memory phenotype CD4 T cells undergoing rapid, nonburst-like, cytokine-driven proliferation can be distinguished from antigen-experienced memory cells.
Memory phenotype (CD44(bright), CD25(negative)) 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.
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Souheil-Antoine
SA
Younes
George
G
Punkosdy
Stephane
S
Caucheteux
Tao
T
Chen
Zvi
Z
Grossman
William E
WE
Paul
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects*; D016207:Cytokines / Q000276:immunology*; D005856:Germ-Free Life; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000276:immunology
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D019394:Ki-67 Antigen; C498355:Mki67 protein, mouse; D011948:Receptors, Antigen, T-Cell; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain; D001973:Bromodeoxyuridine