T-follicular helper cells survive as long-term memory cells.
T-follicular helper (TFH) cells represent the subpopulation of CD4(+)  T cells that provides help for antigen-specific B cells in the GC response. They are generated from naïve T cells during an immune response and are imprinted by their master transcription factor Bcl-6. It has been a long-standing question if TFH cells contribute to the CD4(+)  memory pool after the GC response has been terminated. To answer this question, we sorted antigen-specific TFH and non-TFH effector cells from an ongoing GC response and transferred them into naïve mice. Without further signals via the TCR, transferred cells rapidly contracted with a small population of both TFH and non-TFH cells surviving as memory cells in peripheral lymphoid organs for at least 4 weeks in the absence of antigen. TFH cells strongly downregulated their signature genes Bcl-6, CXCR5, and PD-1 in the memory phase. Upon rechallenge with antigen they rapidly upregulated these markers again. An enhanced potential to produce IL-21, paired with higher expression of CXCR5 and lower expression of CCR7, should enable TFH memory cells to provide more efficient help for antigen-specific B cells than their non-TFH counterparts.
Chronic Immune Reactions, German Rheumatism Research Centre Berlin, DRFZ, Leibniz Institute, Berlin, Germany.
Jan P
JP
Weber
Franziska
F
Fuhrmann
Andreas
A
Hutloff
D019264:Adoptive Transfer; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000276:immunology; D002454:Cell Differentiation; D015536:Down-Regulation; D018858:Germinal Center / Q000276:immunology; D007156:Immunologic Memory; D007378:Interleukins / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D061026:Programmed Cell Death 1 Receptor; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000096:biosynthesis* / Q000276:immunology; D054400:Receptors, CCR7 / Q000096:biosynthesis; D054380:Receptors, CXCR5 / Q000096:biosynthesis* / Q000276:immunology; D013154:Spleen / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D015854:Up-Regulation; D000098546:Interleukin-21
D000943:Antigens, Differentiation; C513179:CXCR5 protein, mouse; C515371:Ccr7 protein, mouse; D007378:Interleukins; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D051560:Proto-Oncogene Proteins c-bcl-6; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D000098546:Interleukin-21