APCs expressing high levels of programmed death ligand 2 sustain the development of CD4 T cell memory.
The role APCs play in the transition of T cells from effector to memory remains largely undefined. This is likely due to the low frequency at which long-lived T cells arise, which hinders analysis of the events involved in memory development. In this study, we used TCR transgenic T cells to increase the frequency of long-lived T cells and developed a transfer model suitable for defining the contribution of APCs to the development of CD4 T cell memory. Accordingly, naive TCR transgenic T cells were stimulated in vitro with Ag presented by different types of APCs and transferred into MHC class II-deficient mice for parking, and the hosts were later analyzed for long-lived T cell frequency or challenged with suboptimal dose of Ag, and the long-lived cells-driven memory responses were measured. The findings indicate that B cells and CD8alpha(+) dendritic cells sustained elevated frequencies of long-lived T cells that yielded rapid and robust memory responses upon rechallenge with suboptimal dose of Ag. Furthermore, both types of APCs had significant programmed death (PD) ligand 2 expression prior to Ag stimulation, which was maintained at a high level during presentation of Ag to T cells. Blockade of PD ligand 2 interaction with its receptor PD-1 nullified the development of memory responses. These previously unrecognized findings suggest that targeting specific APCs for Ag presentation during vaccination could prove effective against microbial infections.
Ellis
Jason S
JS
Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65212, USA.
Guloglu
F Betul
FB
Tartar
Danielle M
DM
Hoeman
Christine M
CM
Haymaker
Cara L
CL
Cascio
Jason A
JA
Wan
Xiaoxiao
X
Dhakal
Mermagya
M
VanMorlan
Amie
A
Yahng
Seung-Hi
SH
Zaghouani
Habib
H
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002645:Chickens; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D000949:Histocompatibility Antigens Class II; D036341:Intercellular Signaling Peptides and Proteins; C111390:OVA 323-339; C105992:PDCD1 protein, human; C556977:PDCD1LG2 protein, human; C556978:Pdcd1lg2 protein, mouse; D010446:Peptide Fragments; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D010047:Ovalbumin