Journal
JOURNAL OF IMMUNOLOGY
Volume 174, Issue 10, Pages 5950-5958Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.174.10.5950
Keywords
-
Categories
Funding
- NCI NIH HHS [CA23108] Funding Source: Medline
- NCRR NIH HHS [P20RR16437] Funding Source: Medline
- NIAID NIH HHS [AI007519, R01AI053056] Funding Source: Medline
- NIAMS NIH HHS [T32AR007576] Funding Source: Medline
Ask authors/readers for more resources
TGF-beta 1 plays a critical role in restraining pathogenic Th1 autoimmune responses in vivo, but the mechanisms that mediate TGF-beta 1's suppressive effects on CD4(+) T cell expression of IFN-gamma expression remain incompletely understood. To evaluate mechanisms by which TGF-beta 1 inhibits IFN-gamma expression in CD4(+) T cells, we primed naive wild-type murine BALB/c CD4(+) T cells in vitro under Th1 development conditions in the presence or the absence of added TGF-beta 1. We found that the presence of TGF-beta 1 during priming of CD4(+) T cells suppressed both IFN-gamma expression during priming as well as the development of Th1 effector cells expressing IFN-gamma at a recall stimulation. TGF-beta 1 inhibited the development of IFN-gamma-expressing cells in a dose-dependent fashion and in the absence of APC, indicating that TGF-beta 1 can inhibit Th1 development by acting directly on the CD4(+) T cell. During priming, TGF-beta 1 strongly inhibited the expression of both T-bet (T box expressed in T cells) and Stat4. We evaluated the importance of these two molecules in the suppression of IFN-gamma expression at the two phases of Th1 responses. Enforced expression of T-bet by retrovirus prevented TGF-beta 1's inhibition of Th1 development, but did not prevent TGF-beta 1's inhibition of IFN-gamma expression at priming. Conversely, enforced expression of Stat4 partly prevented TGF-beta 1's inhibition of IFN-gamma expression during priming, but did not prevent TGF-beta 1's inhibition of Th1 development. These data show that TGF-beta 1 uses distinct mechanisms to inhibit IFN-gamma expression in CD4(+) T cells at priming and at recall.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available