Elimination of IgE regulatory rat CD8+ T cells in vivo increases the co-ordinate expression of Th2 cytokines IL-4, IL-5 and IL-10.
Immunization of rats with soluble antigen (ovalbumin) and the castor bean toxin, ricin, eliminates a subpopulation of CD8+ T cells which suppress IgE responses in vivo. This treatment also reduces the ability of splenic T cells to produce interferon-gamma (IFN-gamma) and enhances their capacity to make interleukin-4 (IL-4). In this report we describe the effect of immunization with ricin and antigen on the expression of mRNA for other T-helper type 2 (Th2) cytokines--IL-5 and IL-10--and their relationship to serum IgE and IL-4 mRNA expression. Splenocytes were taken from rats at different times after immunization with antigen or ricin and antigen and activated in vitro with phorbol myristate acetate (PMA) and ionomycin for 6 hr and total RNA extracted and reverse transcribed. Cytokine gene expression was detected using a quantitative polymerase chain reaction (PCR). Expression of IL-4, IL-5, and IL-10 was increased 7-20-fold 11 days after immunization with ricin and antigen (from 0.107% to 0.769% beta-actin for IL-4, from 0.0167% to 0.381% beta-actin for IL-5, and from 0.0581% to 0.954% beta-actin for IL-10), and preceded maximum serum IgE levels by 4-5 days. There was no increase in IgE or mRNA for these cytokines in rats immunized with antigen alone. The level of IL-4, IL-5, and IL-10 expression declined rapidly after 12 days. Our results suggest that immunization with antigen and ricin preferentially induces a Th2 response, and that CD8+ T cells may play a part in down-regulating the development of Th2 T cells.
Noble
A
A
Department of Allergy and Allied Respiratory Disorders, United Medical School, Guy's Hospital, London, U.K.
Staynov
D Z
DZ
Diaz-Sanchez
D
D
Lee
T H
TH
Kemeny
D M
DM
D000818:Animals; D001483:Base Sequence; D016827:CD8 Antigens / Q000032:analysis*; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007378:Interleukins / Q000032:analysis* / Q000235:genetics; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012276:Ricin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D016827:CD8 Antigens; D007378:Interleukins; D012333:RNA, Messenger; D007073:Immunoglobulin E; D010047:Ovalbumin; D012276:Ricin