Memory programming in CD8(+) T-cell differentiation is intrinsic and is not determined by CD4 help.
CD8(+) T cells activated without CD4(+) T-cell help are impaired in memory expansion. To understand the underlying cellular mechanism, here we track the dynamics of helper-deficient CD8(+) T-cell response to a minor histocompatibility antigen by phenotypic and in vivo imaging analyses. Helper-deficient CD8(+) T cells show reduced burst expansion, rapid peripheral egress, delayed antigen clearance and continuous activation, and are eventually exhausted. Contrary to the general consensus that CD4 help encodes memory programmes in CD8(+) T cells and helper-deficient CD8(+) T cells are abortive, these cells can differentiate into effectors and memory precursors. Importantly, accelerating antigen clearance or simply increasing the burst effector size enables generation of memory cells by CD8(+) T cells, regardless of CD4 help. These results suggest that the memory programme is CD8(+) T-cell-intrinsic, and provide insight into the role of CD4 help in CD8(+) T-cell responses.
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea.
Juhyun
J
Kim
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea.
Su
S
Jeong Ryu
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea.
Keunhee
K
Oh
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea.
Ji-Min
JM
Ju
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea.
Ji
J
Yeong Jeon
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea.
Giri
G
Nam
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea.
Dong-Sup
DS
Lee
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea.
Hang-Rae
HR
Kim
Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea.
Joo
J
Young Kim
Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea.
Jun
J
Chang
The Jackson Laboratory, Bar Harbor, Maine ME04609, USA.
Thomas
T
Sproule
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea.
Kyungho
K
Choi
The Jackson Laboratory, Bar Harbor, Maine ME04609, USA.
Derry
D
Roopenian
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea.
Eun
E
Young Choi
D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000502:physiology; D007156:Immunologic Memory / Q000502:physiology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008863:Microspheres; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D012313:RNA / Q000235:genetics / Q000378:metabolism
D000906:Antibodies; D015778:Minor Histocompatibility Antigens; C114735:minor H antigen H60; D012313:RNA; D007371:Interferon-gamma