Fas ligand expression on T cells is sufficient to prevent prolonged airway inflammation in a murine model of asthma.
Our previous studies revealed that, in a murine model of asthma, mice that received Fas-deficient T cells developed a prolonged phase of airway inflammation, mucus production, and airway hyperreactivity that failed to resolve even 6 weeks after the last challenge. To investigate how Fas-Fas ligand (FasL) interaction occurs between T cells and other cells in vivo, Gld mice with abnormalities of the FasL signaling pathway were used. The reconstituted mice were made by transferring T cells from B6 or Gld mice to Rag(-/-) or FasL-deficient Rag(-/-) mice. We found that Rag(-/-) mice that received B6 T cells resolved the airway inflammation, whereas FasL-deficient Rag(-/-) mice that received Gld T cells developed a prolonged airway inflammation at Day 28, with decreased IFN-gamma production. Both FasL-deficient Rag(-/-) mice that received B6 T cells and Rag(-/-) mice that received Gld T cells also had completely resolved their airway inflammation by Day 28 after challenge. Interestingly, FasL-deficient Rag(-/-) mice that received Gld T cells eventually resolved airway inflammation at Day 42, with a similar level of IFN-gamma production to that of control group. These results demonstrate that FasL expression on either T cells only or non-T cells only was sufficient for the eventual resolution of airway inflammation, and the prolonged airway inflammation in FasL-deficient Rag(-/-) mice that received Gld T cells was correlated with decreased IFN-gamma production by Gld T cells.
Tong
Jiankun
J
Department of Medicine, University of Chicago, IL 60637, USA. jtong@medicine.bsd.uchicago.edu
Clay
Bryan S
BS
Ferreira
Caroline M
CM
Bandukwala
Hozefa S
HS
Moore
Tamson V
TV
Blaine
Kelly M
KM
Williams
Jesse W
JW
Hoffman
Lisa M
LM
Hamann
Kimm J
KJ
Shilling
Rebecca A
RA
Weinstock
Joel V
JV
Sperling
Anne I
AI
D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000502:physiology*; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012137:Respiratory System / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000637:transplantation
D016207:Cytokines; D053222:Fas Ligand Protein; D018398:Homeodomain Proteins; C064658:RAG-1 protein