Generation of rat MHC class-I-restricted ovalbumin-specific IgE inhibitory CD8+ T cell clones.
Allergic disease presents an increasing health problem in industrialised countries. Despite improved diagnosis and drug therapy, the number of fatalities from asthma and anaphylaxis continues to rise. A key element in the aetiology of the allergic response to inert protein antigens is an inherent imbalance in the atopic allergen specific CD4+ T cells, resulting in a dominance of the pathological, IL-4 producing, T helper 2 phenotype which favours B cell IgE production. Previous work from our laboratory, and elsewhere, has established that CD8+ T cells play an important role in regulating the magnitude and duration of IgE responses and may be vital for the restoration of IgE immunologic homoeostasis in 'normal' non-atopic humans and low/medium responder rodents. We have found that CD8+ T cell depletion during a critical period after immunization produces a high and persistent IgE response in otherwise IgE hyporesponsive animals. We and others have demonstrated that small, but important, quantities of soluble antigen can enter the MHC class I pathway and, using ovalbumin (OVA)-transfected antigen-presenting cells, have succeeded in cloning OVA-specific, MHC class I-restricted rat alpha/beta T cell receptor (TcR) positive CD8+ T cells. These cells universally secrete IFN-gamma (5-69 ng/ml) and IL-2 (7.6-37.0 U/ml) and occasionally IL-4 (16.0-8/1.0 IU). When adoptively transferred, 1 x 10(6) of these cloned cells inhibit IgE production in vivo by as much as 50-fold and this effect can be titrated down to 1 x 10(3) cells. The IgE regulatory activity of the clones appears unrelated to their cytolytic potential or to their capacity to make IFN-gamma.
MacAry
P A
PA
Department of Immunology, King's College School of Medicine and Dentistry, Rayne Institute, London, UK.
Holmes
B J
BJ
Kemeny
D M
DM
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002999:Clone Cells; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis; D010047:Ovalbumin / Q000276:immunology*; D051381:Rats
D015395:Histocompatibility Antigens Class I; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin