OX40 drives protective vaccinia virus-specific CD8 T cells.
J Immunol
; 181(11): 7969-76, 2008 Dec 01.
Article
in En
| MEDLINE
| ID: mdl-19017988
ABSTRACT
Vaccinia virus (VACV) affords long-lasting protection against variola virus, the agent of smallpox. VACV-reactive CD8 T cells contribute to protection but their molecular control is unknown. We show that the TNFR molecule OX40 (CD134) controls primary VACV-specific CD8 T cell expansion and antiviral cytokine production and dictates development of strong memory to both dominant and subdominant VACV epitopes. Using adoptive transfer of OX40-deficient CD8 TCR-transgenic T cells responding to Ag in the context of VACV infection, we found that this reflects a direct action of OX40 expressed by CD8 T cells. Furthermore, CD8 T cells that can protect against lethal VACV challenge do not develop in mice deficient in OX40. Thus, OX40, which has been found to play little if any role in the generation of CD8 T cells to several viruses, including lymphocytic choriomeningitis virus and influenza, plays a dominant role in shaping the CD8 T cell response to VACV. These data suggest that unique costimulatory pathways might control alternate antiviral CD8 responses, demonstrating the plasticity of the immune response in utilizing different mechanisms to achieve similar ultimate goals.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vaccinia virus
/
Cytokines
/
CD8-Positive T-Lymphocytes
/
Receptors, OX40
/
Immunologic Memory
Limits:
Animals
Language:
En
Journal:
J Immunol
Year:
2008
Document type:
Article
Affiliation country:
United States