Interferon-gamma-dependent inhibition of late allergic airway responses and eosinophilia by CD8+ gammadelta T cells.
We have previously shown that CD8(+)gammadelta T cells decrease late allergic airway responses, airway eosinophilia, T helper 2 cytokine expression and increase interferon-gamma (IFN-gamma) expression. We hypothesized that the effects of CD8(+)gammadelta T cells were IFN-gamma mediated. Brown Norway rats were sensitized to ovalbumin on day 1. Cervical lymph node CD8(+)gammadelta T cells from sensitized animals were treated with antisense oligodeoxynucleotide (5 micromol/l) to inhibit IFN-gamma synthesis or control oligodeoxynucleotide and 3.5 x 10(4) CD8(+)gammadelta T cells were injected intraperitoneally into sensitized recipients on day 13. Rats were challenged with aerosolized ovalbumin on day 15 and lung resistance was monitored over an 8 hr period, after which bronchoalveolar lavage was performed. Control oligodeoxynucleotide treated gammadelta T cells decreased late airway responses and eosinophilia in bronchoalveolar lavage. There was a complete recovery of late airway responses and a partial recovery of airway eosinophilia in recipients of antisense oligodeoxynucleotide treated cells. Macrophage ingestion of eosinophils was frequent in rats administered gammadeltaT cells but reduced in recipients of antisense oligodeoxynucleotide treated cells. These results indicate that CD8(+)gammadelta T cells inhibit late airway responses and airway eosinophilia through the secretion of IFN-gamma. Defective or altered gammadelta T-cell function may account for some forms of allergic asthma.
Isogai
Susumu
S
Meakins Christie Laboratories, Department of Medicine, McGill University, Montreal, Québec, Canada.
Athiviraham
Aravind
A
Fraser
Russell S
RS
Taha
Rame
R
Hamid
Qutayba
Q
Martin
James G
JG
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003545:Cysteine / Q000378:metabolism; D047093:Eosinophil Major Basic Protein / Q000378:metabolism; D004802:Eosinophilia / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D015289:Leukotrienes / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology; D008297:Male; D020319:Oligodeoxyribonucleotides, Antisense; D010047:Ovalbumin / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000941:Antigens; D015289:Leukotrienes; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; C112381:cysteinyl-leukotriene; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; D047093:Eosinophil Major Basic Protein; D003545:Cysteine