Germinal center helper T cells are dual functional regulatory cells with suppressive activity to conventional CD4+ T cells.
Germinal center (GC) reaction is a T cell-dependent process in which activated B cells mature to produce high-affinity Abs and differentiate into memory B cells. The GC microenvironment is almost exclusively reserved for the optimal Ag-specific B cell clonal expansion, selection, and maturation, but lack significant conventional CD4(+) T cell responses. The mechanisms that ensure such a focused B cell response in the GC are not known. In this study, we report that human CD4(+)CD57(+) T cells, which are the major helper T cells in GCs, actively suppress the activation of conventional CD4(+) T cells, particularly Th1 cells, via a direct contact-dependent mechanism and soluble mediators. Our findings demonstrate that GC T cells are unique regulatory cells that provide critical help signals for B cell response but suppress conventional effector T cells in the same local environment.
Marinova
Ekaterina
E
Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Han
Shuhua
S
Zheng
Biao
B
D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D001402:B-Lymphocytes / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018959:CD57 Antigens / Q000032:analysis; D060908:CTLA-4 Antigen; D002450:Cell Communication; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000502:physiology; D018858:Germinal Center / Q000502:physiology*; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology; D017475:Receptors, Nerve Growth Factor / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018959:CD57 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D053222:Fas Ligand Protein; D053450:Glucocorticoid-Induced TNFR-Related Protein; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; D016212:Transforming Growth Factor beta; D019014:fas Receptor; D016753:Interleukin-10