Elimination of IgE regulatory rat CD8+ T cells in vivo differentially modulates interleukin-4 and interferon-gamma but not interleukin-2 production by splenic T cells.
Intraperitoneal immunization of Hooded Lister rats with a soluble antigen such as bee venom phospholipase A2 (PLA2), or ovalbumin (OVA) together with the toxic lectin, ricin, eliminates a population of early-activated CD8+ T cells which regulate IgE production. These early-activated CD8+ T cells are eliminated because they bear increased ricin-binding glycoproteins on their surface. This immunization regimen produces a vigorous and long-lived IgE response. The effect of this treatment on the capacity of splenic T cells to secrete interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and to generate IL-4 RNA message was assessed. IFN-gamma production by phytohaemagglutinin (PHA)- or ionomycin and phorbol myristate acetate (PMA)-stimulated splenocytes or purified splenic T cells from animals immunized with antigen and ricin was substantially reduced as compared with animals which were given saline or antigen alone (P < 0.001 Student's t-test). At the height of the primary IgE response IFN-gamma production by PHA-stimulated splenocytes was positively correlated with the number of CD8+ T cells (r = 0.90, P < 0.001) and inversely related to the level of serum IgE (r = -0.77, P < 0.020); serum IgE was inversely related to the number of CD8+ T cells (r = -0.92, P < 0.001). The reduced capacity of spleen cells from ricin and antigen immunized rats to produce IFN-gamma was first seen 7 days after immunization. The fall in the ability of splenocytes to secrete IFN-gamma closely paralleled the rise in serum IgE. IL-2 was assayed using an IL-2-dependent cell line which responded to rat IL-2 but not IL-4. Production of IL-2 by splenocytes taken from rats immunized with ricin+antigen was not significantly different to that produced by comparable cells obtained from animals immunized with antigen alone or saline. However, the levels of IL-4 mRNA, detected in ionomycin and PMA-stimulated splenocytes using a quantitative polymerase chain reaction (PCR) procedure, were three- to fourfold higher in ricin and antigen immunized animals as compared with control animals. Following boosting with antigen and ricin the levels of IL-4 message detected increased a further three- to fourfold. These data show that the potentiated IgE response produced by immunization with antigen+ricin is associated with a decreased ability of splenocytes to produce IFN-gamma and an increased capacity to make IL-4.
Department of Allergy and Allied Respiratory Disorders, United Medical School, Guy's Hospital, London.
D
D
Diaz-Sanchez
A
A
Noble
D Z
DZ
Staynov
T H
TH
Lee
D M
DM
Kemeny
D000818:Animals; D016827:CD8 Antigens / Q000032:analysis*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000276:immunology; D010741:Phospholipases A / Q000276:immunology; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D012276:Ricin / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D016827:CD8 Antigens; D007376:Interleukin-2; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D012276:Ricin; D010741:Phospholipases A; D054467:Phospholipases A2