Cutting edge: programmed death-1 defines CD8+CD122+ T cells as regulatory versus memory T cells.
Recent convincing data have shown that naturally occurring CD8(+)CD122(+) T cells are also regulatory T cells. Paradoxically, CD8(+)CD122(+) T cells have been well described as memory T cells. Given their critical role in tolerance versus long-term immunity, it is important to reconcile this profound dichotomy. In this study, we reported that CD8(+)CD122(+) T cells contain both programmed death-1 (PD-1)(-) and PD-1(+) populations. It was CD8(+)CD122(+)PD-1(+) T cells, but not their PD-1(-) counterparts, that suppressed T cell responses in vitro and in vivo. This suppression was largely dependent on their production of IL-10. Moreover, the costimulatory signaling of both CD28 and PD-1 is required for their optimal IL-10 production. In contrast, Ag-specific CD8(+)CD122(+)PD-1(-) T cells were bona fide memory T cells. Thus, CD8(+)CD122(+) T cells can be either regulatory T or memory T cells, depending on their PD-1 expression and Ag specificity. This study reconciles previously contradictory findings and has important implications for tolerance induction.
Dai
Hehua
H
Division of Immunology and Microbiology, University of Texas Health Science Center, Tyler, TX 75708, USA.
Wan
Ni
N
Zhang
Shuzi
S
Moore
Yolonda
Y
Wan
Fusheng
F
Dai
Zhenhua
Z
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006085:Graft Survival / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053646:Interleukin-2 Receptor beta Subunit / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D061026:Programmed Cell Death 1 Receptor; D016038:Skin Transplantation; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; C508022:Il2rb protein, mouse; D053646:Interleukin-2 Receptor beta Subunit; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D016753:Interleukin-10