Unified immune modulation by 4-1BB triggering leads to diverse effects on disease progression in vivo
SCIE
SCOPUS
- Title
- Unified immune modulation by 4-1BB triggering leads to diverse effects on disease progression in vivo
- Authors
- Choi, BK; Kim, YH; Choi, JH; Kim, CH; Kim, KS; Sung, YC; Lee, YM; Moffett, JR; Kwon, BS
- Date Issued
- 2011-09
- Publisher
- ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
- Abstract
- 4-1BB (CD137) is a powerful T-cell costimulatory molecule in the treatment of virus infections and tumors, but recent studies have also uncovered regulatory functions of 4-1BB signaling. Since 4-1BB triggering suppresses autoimmunity by accumulating indoleamine 2,3-dioxygenase (IDO) in dendritic cells (DCs) in an interferon (IFN)-gamma-dependent manner, we asked whether similar molecular and cellular changes were induced by 4-1BB triggering in virus-infected mice. 4-1BB triggering increased IFN-gamma and IDO, and suppressed CD4(+) T cells, in C57BL/6 mice infected with the type 1 KOS strain of Herpes simplex virus (HSV-1), as it does in an autoimmune disease model. Detailed analysis of the CD4(+) T suppression showed that freshly activated CD62L(high) T cells underwent apoptosis in the early phase of suppression, and CD62L(low) effector/memory T cells in the later phase. Although 4-1 BB triggering resulted in similar cellular changes - increased CD8(+) T and decreased CD4(+) T cells, it had different effects on mortality in mice infected with HSV-1 RE, influenza, and Japanese encephalitis virus (JEV); it increased mortality in influenza-infected mice but decreased it in JEV-infected mice. Since the dominant type of immune cell generated to protect the host was different for each virus - CD4(+) T cells and neutrophils in HSV-1 RE infection, both CD4(+) T and CD8(+). T cells in influenza infection, and a crucial role for B cells in JEV infection, 4-1BB triggering resulted in different therapeutic outcomes. We conclude that the therapeutic outcome of 4-1BB triggering is determined by whether the protective immunity generated against the virus was beneficially altered by the 4-1BB triggering. (C) 2011 Elsevier Ltd. All rights reserved.
- Keywords
- 4-1BB (CD137); CD4(+) T cells; CD8(+) T cells; Costimulation; Suppression; T-CELL RESPONSES; JAPANESE ENCEPHALITIS-VIRUS; DENDRITIC CELLS; MONOCLONAL-ANTIBODIES; EXPRESSION; SURVIVAL; CD8(+); MICE; SUPPRESSION; INFECTION
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/17095
- DOI
- 10.1016/J.CYTO.2011.05.015
- ISSN
- 1043-4666
- Article Type
- Article
- Citation
- CYTOKINE, vol. 55, no. 3, page. 420 - 428, 2011-09
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- There are no files associated with this item.
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