Chemical Denaturation of Ovalbumin Abrogates the Induction of Oral Tolerance of Mouse Reaginic Antibody Responses

The effect of chemical denaturation of ovalbumin (OVA) on the induction of oral tolerance of reaginic antibody responses was studied. Both urea-denatured OVA (UD-OVA) and carboxymethylated UD-OVA (CM-OVA) were purified by centrifugation. When compared with OVA and UD-OVA, CM-OVA had the least sensitizing capacity and allergenicity in IgE responses to OVA. BALB/c IgE, IgG1 and IgG antibody responses were suppressed by OVA, but not by UD-OVA or CM-OVA, fed prior to sensitization with OVA, UD-OVA, or CM-OVA in alum, respectively. The priming effect of specific IgG and IgG1 antibody responses was induced by CM-OVA fed prior to sensitization with OVA or CM-OVA. The proliferation of BALB/c spleen cells and their secretion of T helper type 2 (Th2) cytokines interleukin-4 (IL-4) and IL-5 were also orally tolerized by OVA, but not by denatured OVA. Although denatured OVA is hypoallergenic, the present result indicates that denaturation of a soluble protein prevents the induction of oral tolerance of Th2 responses.     

Effect of sublingual administration with a native or denatured protein allergen and adjuvant CpG oligodeoxynucleotides or cholera toxin on systemic T(H)2 immune responses and mucosal immunity in mice.

BACKGROUND: Sublingual immunotherapy has been recently used for allergic diseases, but its mechanisms are still unclear. OBJECTIVE: To examine the effect of sublingual administration of a native or denatured allergen alone or plus adjuvant on systemic T(H)2 responses and mucosal immunity in mice. METHODS: Naive or sensitized BALB/c mice were sublingually vaccinated biweekly for 3 weeks with ovalbumin (OVA) or urea-denatured OVA (CM-OVA) only or plus adjuvant CpG oligodeoxynucleotides (CpG) or cholera toxin (CT). Two weeks later, their specific serum IgG, IgG1, IgG2a, IgE, and saliva secretory IgA (SIgA) antibody responses and the cytokine profiles of spleen and cervical lymph node cells were investigated. RESULTS: Specific SIgA antibody responses were induced by vaccination with CM-OVA plus CpG or CT. Whereas vaccination with CM-OVA and CpG enhanced T(H)1 responses but inhibited IgE production, vaccination with CT and CM-OVA or OVA increased cervical lymph node cell production of interleukin (IL) 4, IL-5, and IL-6 and serum IgG1 antibody responses. In previously sensitized mice, sublingual vaccination with OVA or CM-OVA plus CT or CpG stimulated mucosal SIgA antibody responses, but did not enhance ongoing IgE antibody responses. CONCLUSIONS: Sublingual vaccination with OVA or CM-OVA plus adjuvant CT or CpG all can induce systemic and mucosal immunity, but CM-OVA plus CpG had the best prophylactic and therapeutic effects on IgE antibody production. It is likely that sublingual vaccines may have a role for the prophylaxis and immunotherapy of allergic reactions.     

Oral administration of bovine whey proteins to mice elicits opposing immunoregulatory responses and is adjuvant dependent

Most studies investigating the induction of oral tolerance (OT) use purified proteins such as ovalbumin (OVA), bovine serum albumin (BSA) and beta-lactoglobulin (beta-LG). Little information is available regarding the induction of OT to a protein mixture, e.g. cow's milk. In this study we compared the regulatory mechanisms induced after the oral administration of a whey protein concentrate (WP) derived from cow's milk following immunization with two different adjuvants, complete Freund's adjuvant (CFA) and alum. OVA was used as a control antigen. Animals were given a single feed of these proteins at an equivalent dose of 1 mg/g body weight before they were immunized seven days later with the antigen in Freund's adjuvant or alum. Delayed type hypersensitivity (DTH) responses were suppressed by both a feed of WP and OVA after immunization with CFA. However, only OVA feeding suppressed antigen specific IgG responses. In an attempt to investigate whether WP would tolerize the more susceptible IgE responses, alum immunization replaced CFA as the adjuvant used for systemic immunizations. WP, after a single feed, significantly primed for DTH and IgE responses indicating oral sensitization to WP. In contrast, OVA suppressed DTH, IgE and IgG responses. Antigen specific proliferation of mononuclear cells was suppressed in mice fed OVA, but primed in those fed with WP. In addition cells taken from sensitized mice fed WP up-regulated levels of specific interleukin (IL) -4, -10 and -12 in vitro whereas these cytokines were suppressed in cultures from tolerant WP fed mice. Global suppression was obtained in cultures from tolerant OVA fed mice. TGF-beta was not detected in draining PLN cell cultures of either tolerant or sensitized mice. These data suggest that a whey protein mixture induces divergent responses following immunization with either CFA or alum despite being fed at an identical dose. We suggest that that the choice of the adjuvant may determine the immunoregulatory outcome and this is also reflected by the systemic cytokine profile.     

口服S抗原对抗原诱导性葡萄膜视网膜炎影响的实验研究

目的:观察口服牛视网膜S抗原对Wistar大鼠抗原诱导性葡萄膜视网膜炎(ATU)的影响。方法:用纯化牛视网膜S抗原和福氏完全佐剂的混合乳剂致敏大鼠,14d后接种S抗原于致敏鼠眼玻璃体腔复制AIU模型。观察致敏前后口服S抗原或牛血清白蛋白(BSA)对AIU眼部表现,组织学改变、血清抗体效价、迟发型超敏反应(DTH)、淋巴细胞增殖反应的影响。结果:致敏前后口服BSA对AIU的炎性反应和免疫反应无影响。与口服BSA组比较,预口服S抗原组在AIU第1、3、5d的临床分级参数显著降低,炎症持续时间显著缩短,组织炎性细胞浸润显著减轻,血清特异性抗体滴度降低,DTH显著降低,受S抗原刺激的脾淋巴细胞增殖反应显著降低,加入IL-2共孵育后S抗原刺激的淋巴细胞增殖反应增高。致敏后口服S抗原组在AIU第5d的临床分级参数、炎症持续时间和DTH显著降低,血清特异性抗体滴度降低。结论:口服S抗原可以抑制AIU的炎性反应、细胞免疫反应和体液免疫反应。     

Suppression of an established DTH response to ovalbumin in mice by feeding antigen after immunization

Experiments were designed to examine whether systemic delayed-type hypersensitivity responses (DTH) to ovalbumin (OVA) can be suppressed when antigen is fed after immunization, and to investigate the immunological mechanisms involved. A single 25 mg feed of OVA given 7 or 14 days after immunization with OVA in complete Freund's adjuvant (CFA) suppressed the DTH response of BDF1 mice, but had no significant effect on the serum IgG antibody response. DTH suppression was greatest when antigen was fed soon after immunization, and became less pronounced as the time interval between feeding and immunization increased. The phenomenon was also demonstrated in mice of the BALB/c strain. Cell transfer experiments suggested that the post-immunization suppression was not due to a population of suppressor cells that have been described previously in association with classical oral tolerance for DTH. We conclude that there are separate and distinct mechanisms for the prevention of induction of DTH by antigen feeding in naive mice and the suppression of expression of DTH in sensitized animals.     

gammadelta T cells regulate mucosally induced tolerance in a dose-dependent fashion

We used gammadelta TCR-deficient (TCRdelta(-/-)) mice to examine the role of gammadelta T cells for induction of mucosal responses and systemic tolerance to high versus low doses of oral antigen. When either TCRdelta(-/-) or TCRdelta(+/+) mice were immunized orally with a high dose of ovalbumin (OVA) prior to parenteral challenge, systemic IgG and IgE antibody responses were markedly reduced in both types of mice, while mucosal IgA responses were reduced only in the TCRdelta(-/-) mice. Reduced T cell proliferative responses and delayed-type hypersensitivity were seen in TCRdelta(-/-) and TCRdelta(+/+) mice given the high dose of OVA. Antigen-induced T(h)1 and T(h)2 cytokine production by splenic CD4(+) T cells was severely inhibited in orally tolerized TCRdelta(-/-) and TCRdelta(+/+) mice. In contrast, while oral tolerance associated with increased levels of IL-10 synthesis was induced by a low dose of OVA in TCRdelta(+/+) mice, the TCRdelta(-/-) mice were not tolerized and failed to produce IL-10. Our findings indicate that gammadelta T cells play a significant immunoregulatory role in IL-10-mediated, low-dose oral tolerance induction, but are not essential participants in the induction of systemic tolerance to orally introduced antigens given in larger doses.     

The kinetics of oral hyposensitization to a protein antigen are determined by immune status and the timing, dose and frequency of antigen administration.

We have investigated the immunological consequences of feeding a protein antigen to previously immunized animals. BALB/c mice were systemically primed with ovalbumin (OVA) in complete Freund's adjuvant (CFA) and fed with high (10 mg/g body weight), medium (1 mg/g body weight) or low (1 microgram/g body weight) doses of OVA once (Day 1, 7 or 14) or sequentially for 5 days (Days 1-5, 7-11, 14-18). The specific IgG antibody response was suppressed only by early feeds of high-dose OVA (Days 1-5). Medium-dose OVA fed on Day 14 or low-dose OVA fed at any stage after immunization enhanced the IgG antibody response. In contradistinction, systemic delayed-type hypersensitivity responses (DTH) were usually suppressed by early feeds of high or medium doses of OVA but never after feeding low-dose OVA. The results suggest that systemic DTH and IgG antibody responses to oral antigen are subject to different control mechanisms in previously primed animals. Such responses depend on the immune status of the animal and are controlled by antigen dose, time and frequency of feeding. The immunological effects observed are also demonstrable following adoptive transfer of spleen cells collected 14 days after multiple feeds of high-dose OVA to immunized mice. Our findings suggest that oral hyposensitization after systemic immunization is regulated by (suppressor) spleen cells which are activated by gut-processed antigen.     

Priming of systemic and local delayed-type hypersensitivity responses by feeding low doses of ovalbumin to mice.

We have examined the effects on both systemic and intestinal immunity of feeding different doses of ovalbumin (OVA) to mice. A single feed of doses of more than 1 mg OVA produced significant suppression of subsequent delayed-type hypersensitivity (DTH) and IgG antibody responses. Feeding 100 micrograms-1 mg OVA had no net effect on systemic immunity, but mice fed 10-50 micrograms OVA had consistently enhanced systemic DTH responses when immunized subsequently with OVA in adjuvant. Oral challenge of these mice with OVA produced alterations in mucosal architecture and in intra-epithelial lymphocyte counts, consistent with the presence of an intestinal DTH response. Similar changes were not found in mice fed tolerogenic doses of OVA. Although feeding low doses of OVA primed both systemic and intestinal DTH responses, this had no effect on serum IgG responses and very little systemic DTH could be revealed in OVA-fed mice without systemic challenge with OVA in adjuvant. We conclude that feeding certain low doses of protein antigens can induce priming of local and systemic DTH responses rather than the immune tolerance which is normally found. The development of clinical food hypersensitivities may be highly dependent on the dose of dietary antigen at the time of first encounter.     

Down-regulation of immune responses to inhaled antigen: studies on the mechanism of induced suppression

Repeated exposure of rats to an aerosol of ovalbumin (OVA) or its dinitrophenylated derivative (DNP-OVA) induced carrier-specific tolerance to subsequent challenge with the same haptenated antigen. Following parenteral challenge with DNP-OVA, both anti-DNP and anti-OVA IgE titres were reduced relative to controls, whereas anti-DNP responses following challenge with DNP-Ascaris were normal. Stimulation of tolerant rats with OVA, together with the polyclonal B-cell mitogen LPS, restored their capacity to respond to the antigen. In contrast to WAG rats, which have previously been shown to develop equivalent tolerance in the IgE an IgG antibody classes (Sedgwick & Holt, 1984), BN rats exposed to an OVA aerosol developed high serum titres of anti-OVA IgG. Following parenteral challenge with DNP-OVA, however, anti-DNP IgG responses in the BNs were markedly reduced relative to unexposed controls, while anti-OVA IgG titres were maintained at a high level. Further strain-dependent differences in T-cell function in tolerized rats appeared in in vivo assays of DTH reactivity and in in vitro antigen-driven lymphocyte proliferation. Both BN and WAG rats displayed diminished in vitro responses, whereas DTH reactions were only suppressed in the latter strain.     

Appearance of delayed-type hypersensitivity effector cells in murine gut mucosa.

Feeding of a protein antigen, human gamma globulin (HGG), to BALB/c mice prior to parenteral immunization resulted in the abrogation of a delayed-type hypersensitivity (DTH) response to challenge with that antigen. Unlike parenterally immunized mice, HGG-fed mice were unable to transfer DTH to naive syngeneic recipients using peripheral lymph node lymphocytes. Co-transfer experiments ruled out the possibility of a suppressor cell in the orally immunized mice operating on DTH effector cells. Intra-epithelial lymphocytes (IELs) from mice immunized either orally or parenterally were able to transfer a DTH reaction to unimmunized recipients, while mesenteric lymph node lymphocytes from orally, but not parenterally, immunized donors were capable of transferring DTH. The implications of these results for investigations of gastrointestinal disorders with a suspected immunological aetiology are discussed.     

Studies on the immunogenicity of an endogenously processed protein antigen in mice

We have examined the general immunogenicity of a non-replicating antigen which was introduced artificially into the endogenous pathway of antigen processing. EG7.OVA cells transfected with the OVA gene are efficient presenters of endogenously processed OVA and induced high levels of class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) in vivo. In addition, mice immunised with EG7.OVA cells developed immune responses more characteristic of class II MHC-restricted T cells, including IgG antibody production, systemic delayed type hypersensitivity (DTH) and a proliferative response to OVA in vitro. However, most of these responses were small, and EG7.OVA cells did not prime mice for secondary antibody or DTH responses. Thus endogenously synthesised, non-replicating antigens are poor stimulators of T cells which exploit the exogenous processing pathway. If vaccine vectors containing purified epitopes are to stimulate all T cells effectively, they will need to utilise strategies which enable direct entry to both antigen processing pathways.     

Bystander suppression of the immune response to human serum albumin in rats fed ovalbumin.

Bystander suppression of delayed-type hypersensitivity (DTH) and the antibody response to human serum albumin (HSA) were studied in young normal rats and in young rats made partially tolerant to ovalbumin (OVA) by feeding an OVA-containing diet for 4 weeks from weaning. At 2 months of age, the animals were intracutaneously immunized with a mixture of OVA and HSA in Freund's complete adjuvant (FCA) at one site of the back, or separately at two different sites on the back. All rats made orally tolerant to OVA showed a significantly reduced IgE and IgG anti-OVA antibody production and DTH response to OVA, compared to the controls. OVA-fed rats subsequently immunized with a mixture of OVA + HSA had significantly lower IgE and DTH responses to HSA than the controls. When rats were immunized with OVA and HSA at two different sites, however, there was no difference in the response to HSA between the OVA-fed rats and the control rats, which rules out the possibility of shared epitopes between the antigens. Ear-challenge with the mixture of OVA + HSA gave a significantly lower DTH reaction in the tolerant rats immunized with a mixture of the antigens, compared to the control rats. However, suppression of the DTH reaction was not seen when tolerant and control rats were immunized with HSA alone and challenged with the mixture of OVA + HSA in one ear. These results present evidence that young rats orally tolerant to one antigen show a suppressed T-cell and antibody response to an unrelated antigen, provided that the two antigens are given in a mixture during the inductive phase. There was no evidence for bystander suppression of the T-cell response at the effector site.     

Denaturation of ovalbumin abrogates oral induction of airway hyperreactivity and IgG1, IgG2 antibody responses in guinea pigs

BACKGROUND: The effects of denaturation of ovalbumin (OVA) on the induction of oral sensitization in guinea pigs were examined. METHODS: Guinea pig antibody and airway responses were assessed after 10 feedings of chemically or heat-denatured OVA or egg white (EW). RESULTS: Their specific IgG, IgG1 and IgG2 antibody responses were orally sensitized by OVA or EW, but not by chemically or heat-denatured OVA or EW. When further exposed to 0.1% OVA or conalbumin aerosol, those fed OVA or EW, but not denatured OVA or EW, had increased pulmonary resistance and decreased tidal volume. On the other hand, in those fed denatured OVA, boiled EW or saline only, a second sensitization with 1% OVA aerosol generated antibody responses and airway hyperreactivity. Using a sandwich ELISA, guinea pig serum OVA was detected after feeding EW, but not chemically denatured or boiled EW. CONCLUSIONS: It is likely that guinea pig gut absorption of OVA may result in oral sensitization. Chemical or heat denaturation of proteins may minimize their intestinal uptake and thus abrogates the induction of oral sensitization in guinea pigs.     

Effect of neonatal sublingual vaccination with native or denatured ovalbumin and adjuvant CpG or cholera toxin on systemic and mucosal immunity in mice

Sublingual immunotherapy has been applied for allergic diseases, but whether sublingual immunization in neonates can prevent sensitization has not been studied. In this study, we evaluate the effect of neonatal sublingual vaccination with native or denatured allergens alone or plus adjuvant on allergy prevention. Newborn BALB/ c mice were sublingually vaccinated daily for the first 3 days with native or denatured ovalbumin (OVA) only, or combined adjuvant CpG or cholera toxin (CT). They were sensitized with OVA adsorbed onto alum 7 weeks after the last vaccination. Specific secretory IgA antibody responses were readily induced by neonatal vaccination with antigen plus CpG or CT, but not with antigen alone. Whereas vaccination with denatured OVA plus CpG markedly enhanced T helper 1 (Th1) responses and inhibited IgE production, vaccination with denatured OVA plus CT increased cervical lymph node cell production of interleukin-4 (IL-4), IL-5, IL-6, and serum IgG1 responses. These data demonstrate that neonatal sublingual vaccination with denatured OVA and CpG not only preferentially induces systemic Th1 responses and mucosal immunity, but also simultaneously abrogates IgE production. Neonatal sublingual vaccines may play a role for the strategy of allergy prevention.     

Impaired antigen‐specific lymphocyte priming in mice after Toll‐like receptor 4 activation via induction of monocytic myeloid‐derived suppressor cells

In sepsis, the pathology involves a shift from a proinflammatory state toward an immunosuppressive phase. We previously showed that an agonistic anti‐TLR4 antibody induced long‐term endotoxin tolerance and suppressed antigen‐specific secondary IgG production when primed prior to immunization with antigen. These findings led us to speculate that TLR4‐induced innate tolerance due to primary infection causes an immunosuppressive pathology in sepsis. Therefore, the mechanism underlying impaired antigen‐specific humoral immunity by the TLR4 antibody was investigated. We showed, in a mouse model, that primary antigen‐specific IgG responses were impaired in TLR4 antibody‐induced tolerized mice, which was the result of reduced numbers of antigen‐specific GC B cells and plasma cells. Ovalbumin‐specific CD4 and CD8 T‐cell responses were impaired in TLR4 antibody‐injected OT‐I and ‐II transgenic mice ex vivo. Adoptive transfer studies demonstrated suppression of OVA‐specific CD4 and CD8 T‐cell responses by the TLR4 antibody in vivo. The TLR4 antibody induced Gr1⁺CD11b⁺ myeloid‐derived suppressor cell (MDSC) expansion with suppression of T‐cell activation. Monocytic MDSCs were more suppressive and exhibited higher expression of PD‐L1 and inducible nitric oxidase compared with granulocytic MDSCs. In conclusion, immune tolerance conferred by TLR4 activation induces the expansion of monocytic MDSCs, which impairs antigen‐specific T‐cell priming and IgG production.     

The role of antigen recognition and suppressor cells in mice with oral tolerance to ovalbumin.

The induction of tolerance by feeding proteins may prevent potentially harmful delayed-type hypersensitivity (DTH) reactions to food antigens. Suppressor T cells (Ts) are present in mice with tolerance of systemic DTH after feeding ovalbumin (OVA) but, as other immunoregulatory mechanisms have also been described, the exact role of Ts in maintaining tolerance is not known. In this study, we have used the ability of native and denaturated OVA to cross-react at the level of helper/effector T cells, but not Ts, to re-examine the role of Ts in oral tolerance to OVA. Mice immunized with native OVA (nOVA) or denatured OVA (dOVA) in adjuvant had fully cross-reacting DTH to either nOVA or dOVA, but intravenous administration of antigen induced Ts which were specific for the appropriate form. Mice fed nOVA or dOVA had identical tolerance of systemic DTH to both forms of OVA, and feeding nOVA induced splenic Ts which suppressed the DTH response to both nOVA and dOVA. Splenic Ts could not be detected in mice fed dOVA. The results support the hypothesis that tolerance of systemic DTH in mice fed native proteins is due to Ts. Although, for the moment, there is no complementary evidence for a role for Ts in oral tolerance to denatured proteins, this study is consistent with the idea that Ts are the mechanism which normally prevent enteropathy due to DTH against dietary proteins. In addition, our study underlines the differences between orally and parenterally induced Ts and reinforces the view that fed proteins induce Ts after processing by the gut or its lymphoid accessory cells.     

Importance of gastrointestinal ingestion and macromolecular antigens in the vein for oral tolerance induction

Oral administration of a certain dose of antigen can generally induce immunological tolerance against the same antigen. In this study, we showed the temporal appearance of ovalbumin (OVA) antigens in both portal and peripheral blood of mice after the oral administration of OVA. Furthermore, we detected 45,000 MW OVA in mouse serum 30 min after the oral administration of OVA. Based on this observation, we examined whether the injection of intact OVA into the portal or peripheral vein induces immunological tolerance against OVA. We found that the intravenous injection of intact OVA did not induce immunological tolerance but rather enhanced OVA-specific antibody production in some subclasses, suggesting that OVA antigens via the gastrointestinal tract but not intact OVA may contribute to establish immunological tolerance against OVA. Therefore, we examined the effects of digesting intact OVA in the gastrointestinal tract on the induction of oral tolerance. When mice were orally administered or injected into various gastrointestinal organs, such as the stomach, duodenum, ileum, or colon and boosted with intact OVA, OVA-specific antibody production and delayed-type hypersensitivity (DTH) response were significantly enhanced in mice injected into the ileum or colon, compared with orally administered mice. These results suggest that although macromolecular OVA antigens are detected after oral administration of OVA in tolerant-mouse serum, injection of intact OVA cannot contribute to tolerance induction. Therefore, some modification of macromolecular OVA in the gastrointestinal tract and ingestion may be essential for oral tolerance induction.     

Cell-mediated and humoral immune responses in mice. IV. Difference of the functional cell population between helper activity and delayed-type hypersensitivity.

Helper activity in the anti-hapten antibody response was studied in mice in reference to the induction of delayed-type hypersensitivity (DTH) to the carrier protein. Mice were immunized either by an i.v. injection of alum-precipitated bovine serum albumin (AP-BSA) plus bacterial endotoxin or by a s.c. injection of BSA in Freund's complete adjuvant, the latter being effective in inducing DTH. The helper activity was estimated by the antibody response to the challenge with dinitrophenylated BSA (DNP-BSA) given at varying intervals after the injection of BSA. The results indicated that the helper activity was independent of DTH to the carrier protein, suggesting that these two activities, are mediated by different populations of functional cells. A low dose of tolerogenic soluble BSA (sBSA) was sufficient to abrogate the helper activity in the response to DNP-BSA. In contrast, DTH to BSA was only partially depressed by the pretreatment with a low dose of sBSA and was completely depressed by a high dose. DTH reactivity in mice pretreated with a low dose of tolerogen and followed by the immunization with BSA in Freund's complete adjuvant was substantiated by the microscopic observation of mononuclear cell infiltration at the site of the test antigen injection. These results suggest that cells involved in the helper function and DTH may be derived from different precursors.     

Neonatal colonization of rats induces immunological tolerance to bacterial antigens

We wanted to investigate the immunological events occurring in rats intestinally colonized from birth (neonatally) or at adult age with an ovalbumin (OVA)-producing Escherichia coli O6K13 strain, carrying type 1 pili. The neonatally colonized animals responded with lower delayed type hypersensitivity (DTH) against OVA and lower levels of IgG antibodies against OVA, O6 lipopolysaccharide (LPS) and type 1 pili compared to age-matched controls. The IgG antibody response against the bystander antigen, human serum albumin (HSA), was lower in the neonatally colonized animals than in the controls co-immunized with HSA and E. coli, indicating a release of suppressive factors induced by the bacterial antigens. The adult colonized animals showed an increased DTH and antibody response against OVA after immunization. They also had high pre-immunization levels of IgG anti-O6 LPS antibodies compared to controls. However, the relative increase in IgG anti-O6 LPS antibody levels after the immunization with dead E. coli was much lower in the adult colonized animals. The present results suggest that neonatal animals develop tolerance against antigen on bacterial colonizers of the intestine. In addition, this tolerance contains components of suppression.     

Selective inhibition of systemic anti-OVA IgE production in response to oral pre-treatment with OVA-liposome conjugates

BACKGROUND: We have previously reported that intraperitoneal injection with OVA-liposome conjugates induces OVA-specific and IgE-selective unresponsiveness in mice. METHODS: In the present study, the effects of oral pre-treatment with OVA-liposome conjugates or with plain OVA solution on anti-OVA IgG antibody production were investigated in mice after subsequent immunization with alum-adsorbed OVA. Control mice received only the immunization. RESULTS: The levels of serum anti-OVA IgG antibody in mice receiving oral administration of OVA-liposome were comparable to those in the control mice. However, in mice receiving oral administration of the same dose of plain OVA, levels of serum anti-OVA IgG antibody were significantly lower than those in control mice. Surprisingly, anti-OVA IgE antibody production was completely inhibited in mice receiving oral administration of OVA-liposome conjugates. Splenic CD4(+) T cells of mice receiving oral administration of OVA-liposome and those of control mice produced comparable levels of cytokines, while those of mice receiving oral administration of plain OVA solution produced significantly lower levels of cytokines than those in the other two groups. CONCLUSION: Orally administered OVA-liposome did not affect anti-OVA IgG production but did inhibit anti-OVA IgE antibody production, while orally administered OVA solution inhibited production of both IgG and IgE antibodies. These results suggest that antigen-liposome conjugates can possibly be orally administered in order to control antigen-specific IgE antibody production, without affecting IgG antibody production.