Activation and exhaustion of antigen-specific CD8+T cells occur in different splenic compartments during infection with Plasmodium berghei.
The spleen is the major organ in which T cells are primed during infection with malaria parasites. However, little is known regarding the dynamics of the immune responses and their localization within the splenic tissue during malaria infection. We examined murine CD8+T cell responses during infection with Plasmodium berghei using recombinant parasites expressing a model antigen ovalbumin (OVA) protein and compared the responses with those elicited by Listeria monocytogenes expressing the same antigen. OVA-specific CD8+T cells were mainly activated in the white pulp of the spleen during malaria infection, as similarly observed during Listeria infection. However, the fates of these activated CD8+T cells were distinct. During infection with malaria parasites, activated CD8+T cells preferentially accumulated in the red pulp and/or marginal zone, where cytokine production of OVA-specific CD8+T cells decreased, and the expression of multiple inhibitory receptors increased. These cells preferentially underwent apoptosis, suggesting that T cell exhaustion mainly occurred in the red pulp and/or marginal zone. However, during Listeria infection, OVA-specific CD8+T cells only transiently expressed inhibitory receptors in the white pulp and maintained their ability to produce cytokines and become memory cells. These results highlighted the distinct fates of CD8+T cells during infection with Plasmodium parasites and Listeria, and suggested that activation and exhaustion of specific CD8+T cells occurred in distinct spleen compartments during infection with malaria parasites.
Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan; Program for Nurturing Global Leaders in Tropical and Emerging Infectious Diseases, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan.
Ganchimeg
G
Bayarsaikhan
Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan.
Mana
M
Miyakoda
Division of Cell Function Research Support, Biomedical Research Support Center, School of Medicine, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan.
Kazuo
K
Yamamoto
Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan.
Daisuke
D
Kimura
Program for Nurturing Global Leaders in Tropical and Emerging Infectious Diseases, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan.
Masoud
M
Akbari
Department of Medical Zoology, School of Medicine, Mie University, 2-174, Edobashi, Tsu 514-8507, Japan.
Masao
M
Yuda
Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan; Program for Nurturing Global Leaders in Tropical and Emerging Infectious Diseases, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan. Electronic address: katsu@nagasaki-u.ac.jp.
Katsuyuki
K
Yui
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010962:Plasmodium berghei / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology*
D000953:Antigens, Protozoan; D007371:Interferon-gamma; D010047:Ovalbumin
CD8(+) T cells; Infectious diseases; Inhibitory receptors; Malaria; Spleen