During primary virus infections, innate immune cells sense foreign molecules and, in turn alert and arm effector lymphocytes by secreting pro-inflammatory cytokines. Type I interferons (IFN-a/b) are a class of pro-inflammatory cytokines that are secreted by innate dendritic cells during virus infections. IFN-a/b is important in driving the development of human CD4+ T cells to secrete high levels of IFN-g that promotes the eradication of virally-infected cells. However, in mice, IFN-a/b does not promote the induction of IFN-g secretion from CD4+ T cells because the murine IFN-a/b receptor does not activate the critical down-stream transcription factor, STAT4, required to promote IFN-g secretion. This important pathway is blocked in mice and does not reflect the important role that CD4+ T cells play during virus infections in humans. Our lab has discovered the species-specific component for the human IFN-a/b receptor that promotes STAT4 activation in human CD4+ T cells. Therefore, the goals of this project are 1) To reconstitute IFN-a/b-dependent STAT4 signaling in murine T cells by genetic manipulation, and 2) Determine the role that this pathway plays during in vivo interferon responses in genetically altered mice. ? ? ?
| Chowdhury, Fatema Z; Ramos, Hilario J; Davis, Laurie S et al. (2011) IL-12 selectively programs effector pathways that are stably expressed in human CD8+ effector memory T cells in vivo. Blood 118:3890-900 |
| Huber, Jonathan P; Ramos, Hilario J; Gill, Michelle A et al. (2010) Cutting edge: Type I IFN reverses human Th2 commitment and stability by suppressing GATA3. J Immunol 185:813-7 |
| Ramos, Hilario J; Davis, Ann M; Cole, Alexander G et al. (2009) Reciprocal responsiveness to interleukin-12 and interferon-alpha specifies human CD8+ effector versus central memory T-cell fates. Blood 113:5516-25 |
| Davis, Ann M; Ramos, Hilario J; Davis, Laurie S et al. (2008) Cutting edge: a T-bet-independent role for IFN-alpha/beta in regulating IL-2 secretion in human CD4+ central memory T cells. J Immunol 181:8204-8 |
| Ramos, Hilario J; Davis, Ann M; George, Thaddeus C et al. (2007) IFN-alpha is not sufficient to drive Th1 development due to lack of stable T-bet expression. J Immunol 179:3792-803 |
