IFN-gamma secretion by CD8T cells inhibits allergen-induced airway eosinophilia but not late airway responses.
BACKGROUND
CD8+T cells can suppress allergen-induced late airway responses (LARs) and airway inflammation.


OBJECTIVE
To test the hypothesis that the suppression of LARs and airway eosinophilia by CD8+T cells is IFN-gamma mediated, we tested the effects of adoptively transferred CD8+T cells, in which IFN-gamma synthesis was inhibited by an antisense (AS) oligodeoxynucleotide (ODN), on the airway responses of a rat model of allergic asthma.


METHODS
CD8+T cells were harvested from the cervical lymph nodes of ovalbumin (OVA)-sensitized Brown Norway rats for administration to other actively sensitized syngeneic rats. CD8+T cells (2 x 10(6)) were incubated for 6 hours with 2 micromol/L AS ODN or sense ODN and were injected intraperitoneally into recipients; inhibition of IFN-gamma expression in vitro by AS ODN was shown by means of flow cytometry. Two days later, rats were challenged with aerosolized OVA.


RESULTS
OVA-induced LAR and bronchoalveolar lavage (BAL) fluid eosinophilia were suppressed by sense ODN-treated CD8+T cells. IFN-gamma expression in BAL cells was elevated in these animals. IFN-gamma expression in BAL cells was at control levels in recipients of AS ODN-treated CD8+ cells, confirming the success of the AS treatment in vivo. BAL eosinophilia was also largely restored in the AS ODN treatment group. In contrast, the CD8+T cell-induced suppression of the LAR was not significantly affected by AS ODN pretreatment.


CONCLUSIONS
These results indicate that CD8+T cells inhibit airway eosinophilia through secretion of IFN-gamma but may suppress the LAR by means of other mechanisms.
Suzuki
Masaru
M
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Maghni
Karim
K
Molet
Sophie
S
Shimbara
Ayako
A
Hamid
Qutayba A
QA
Martin
James G
JG
D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001980:Bronchi / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000503:physiopathology*; D001991:Bronchitis / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000637:transplantation; D004802:Eosinophilia / Q000276:immunology / Q000517:prevention & control*; D007371:Interferon-gamma / Q000502:physiology*; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D013997:Time Factors
D000485:Allergens; D016376:Oligonucleotides, Antisense; D007371:Interferon-gamma; D010047:Ovalbumin