Bcl6 acts as an amplifier for the generation and proliferative capacity of central memory CD8+ T cells.
Central memory CD8(+) T cells (T(CM)) are considered to be more efficient than effector ones (T(EM)) for mediating protective immunity. The molecular mechanism involved in the generation of these cells remains elusive. Because Bcl6 plays a role in the generation and maintenance of memory CD8(+) T cells, we further examined this role in the process in relation to T(CM) and T(EM) subsets. In this study, we show that T(CM) and T(EM) were functionally identified in CD62L(+) and CD62L(-) memory (CD44(+)Ly6C(+)) CD8(+) T cell subsets, respectively. Although T(CM) produced similar amounts of IFN-gamma and IL-2 to T(EM) after anti-CD3 stimulation, the cell proliferation capacity after stimulation and tissue distribution profiles of T(CM) differed from those of T(EM). Numbers of T(CM) were greatly reduced and elevated in spleens of Bcl6-deficient and lck-Bcl6 transgenic mice, respectively, and those of T(EM) were constant in nonlymphoid organs of these same mice. The majority of Ag-specific memory CD8(+) T cells in spleens of these mice 10 wk after immunization were T(CM), and the number correlated with Bcl6 expression in T cells. The proliferation of Ag-specific memory CD8(+) T cells upon secondary stimulation was dramatically up-regulated in lck-Bcl6 transgenic mice, and the adoptive transfer experiments with Ag-specific naive CD8(+) T cells demonstrated that some of the up-regulation was due to the intrinsic effect of Bcl6 in the T cells. Thus, Bcl6 is apparently a crucial factor for the generation and secondary expansion of T(CM).
Ichii
Hirohito
H
Department of Developmental Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan.
Sakamoto
Akemi
A
Kuroda
Yoshikazu
Y
Tokuhisa
Takeshi
T
D000818:Animals; D000941:Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D007156:Immunologic Memory / Q000276:immunology / Q000502:physiology*; D008024:Ligands; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000502:physiology*
D000941:Antigens; D004268:DNA-Binding Proteins; D008024:Ligands; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors