Alterations in cytokine production following intraocular injection of soluble protein antigen: impairment in IFN-gamma and induction of TGF-beta and IL-4 production.
Immune deviation induced by intraocular injection of soluble protein Ag, referred to as anterior chamber-associated immune deviation (ACAID), is characterized by impairment of delayed hypersensitivity (DH). Two populations of splenic regulatory cells that impair the induction and expression phases of DH are involved in the ACAID response and may mediate their effects through cytokines. The purpose of the present study was to evaluate the role that cytokines play in ACAID. IFN-gamma production in draining lymph nodes induced by conventional immunization with protein Ag and adjuvant was suppressed after intraocular injection of protein Ag administered either before or after sensitization; IL-12 production in these mice was not decreased, suggesting that suppression of IL-12 may not be the mechanism involved in the impairment in IFN-gamma production. Surprisingly, although significant amounts of IL-4 (but not IL-10) were produced by spleen and lymph node cells from several different strains of mice, experiments in IL-4 knockout mice showed that impairment of neither DH nor IFN-gamma production required IL-4. Interestingly, significant levels of TGF-beta were detected in cultures of spleen cells from mice with ACAID. As determined by quantitative RT-PCR, TGF-beta was produced primarily by the splenic CD4 and non-T cells and was of the TGF-beta1 type. These results suggest that the Th1 response is impaired in ACAID by a mechanism(s) that does not require Th2-type cytokines, but may involve TGF-beta at several different (including the effector) phases during the response.
Kosiewicz
M M
MM
Department of Internal Medicine, Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Alard
P
P
Streilein
J W
JW
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology* / Q000378:metabolism; D000941:Antigens / Q000008:administration & dosage*; D003433:Crosses, Genetic; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D007114:Immunization; D007267:Injections; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D012995:Solubility; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D000941:Antigens; D016207:Cytokines; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin