4-1BB costimulation enhances HSV-1-specific CD8+ T cell responses by the induction of CD11c+CD8+ T cells.
Since 4-1BB plays a predominant role in CD8+ T cell responses, we investigated the effects of 4-1BB triggering on the primary and memory CD8+ T responses to HSV-1 infection. 4-1BB was detected on 10-15% of CD4+ and CD8+ T cells following the infection. 4-1BB-positive T cells were in the proliferative mode and showed the enhanced expression of anti-apoptotic proteins. Agonistic anti-4-1BB treatment exerted preferential expansion of CD8+ T cells and gB/H-2Kb-positive CD8+ T cells, and enhanced cytotoxicity against HSV-1 that was mainly mediated by CD11c+CD8+ T cells. CD11c+CD8+ T cells were re-expanded following re-challenge with HSV-1 at post-infection day 50, indicating that CD11c+CD8+ phenotype was maintained in memory CD8+ T cell pool. Our studies demonstrated that 4-1BB stimulation enhanced both primary and memory anti-HSV-1 CD8+ T cell responses, which was mediated by a massive expansion of antigen-specific CD11c+CD8+ T cells.
Kim
Young H
YH
The Immunomodulation Research Center, University of Ulsan, Ulsan 680-749, Republic of Korea.
Seo
Su K
SK
Choi
Beom K
BK
Kang
Woo J
WJ
Kim
Chang H
CH
Lee
Sun K
SK
Kwon
Byoung S
BS
D053330:4-1BB Ligand; D000818:Animals; D000906:Antibodies / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006561:Herpes Simplex / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048069:Tumor Necrosis Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D017735:Virus Latency
D053330:4-1BB Ligand; D000906:Antibodies; D039521:CD11c Antigen; C505974:TNFSF9 protein, human; C505975:Tnfsf9 protein, mouse; D048069:Tumor Necrosis Factors