ICAM-1 expression on CD8+ T cells negatively regulates IFN-γ production. (50.28)

• Published in: The Journal of immunology (1950) Vol. 184; no. 1_Supplement; pp. 50 - 50.28
• Main Authors: Zumwalde, Nicholas, Shimizu, Yoji
• Format: Journal Article
• Language: English
• Published: 01.04.2010
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.184.Supp.50.28

Abstract The factors that regulate the production of effector cytokines following antigen stimulation of naïve CD8+ T-cells are incompletely characterized. We utilized ICAM-1-/- mice to determine if the expression of ICAM-1 on naïve CD8+ T-cells modulates CD8+ T-cell activation and differentiation. Stimulation of purified wild-type OT-I CD8+ T-cells with purified MHC/Antigen, B7-1, and the inflammatory cytokine IL-12 results in robust proliferation and differentiation into CD8+ effector T-cells producing IFN-γ. This activation is associated with prominent T-cell:T-cell clusters and increased expression of ICAM-1. The presence of IL-12 sustains elevated levels of ICAM-1 on activated CD8+ T-cells and enhances T-cell:T-cell clusters. Activation of ICAM-1-/- OT-I T-cells results in comparable levels of proliferation as wild-type OT-I T-cells. However, ICAM-1-/- CD8+ T-cells fail to form significant homotypic clusters upon activation in this system. In addition, when compared to wild-type OT-I T-cells, antigen-specific activation of ICAM-1-/- OT-I T-cells results in a higher percentage of effector T-cells producing IFN-γ. These results suggest that inflammatory cytokines such as IL-12 may attenuate the generation of IFN-γ+ CD8+ effector T-cells via modulation of ICAM-1 expression following antigen stimulation of naïve CD8+ T-cells.