Administration of interferon-g to pregnant rats reverses the depressed adjuvant-induced arthritis of their chronically Trypanosoma cruzi-infected offspring.

We demonstrated that administration of interferon gamma (IFN-gamma) to the inbred "I" strain of pregnant rats conferred partial resistance on their offspring to challenge with Trypanosoma cruzi. We now examine if this intervention also modifies the reportedly immunodepressed cellular responses which occur during chronic infection. Offspring were born to mothers undergoing one of the following procedures during gestation: subcutaneous injections of recombinant rat IFN-gamma, 50,000 IU/rat, five times/week for 3 weeks, which was started on the day of mating (IFN-Mo); infection with 10(6) trypomastigotes of T. cruzi at 7, 14, and 21 days after mating plus IFN-gamma treatment as given to the former group (TcIFN-Mo); the same protocol except that physiological saline was injected instead of IFN-gamma (Te-Mo); injection of physiological saline only (control-Mo). All offspring groups (N = 8-10/group) were infected at weaning and were assessed 90 days later for their adjuvant-induced arthritic response or levels of major T cell subsets in spleen and lymph nodes. TcIFN-Mo and IFN-Mo offspring showed a reestablished arthritic response, which remained within the range seen in controls. Immunolabeling studies on parallel groups of 90-day-infected offspring showed that the inverse CD4/CD8 cell ratio that is usually seen in lymphoid organs from these chronically infected rats (median 0.61) appeared to have recovered in the TcIFN-Mo and IFN-Mo groups (median 1.66 and 1.78, respectively) and was not different from uninfected controls (1.96). These studies indicate that early stimulation with IFN-gamma is able to reverse the immunosuppressive state that is usually present during the chronic period of the experimental infection.

Administration of interferon-gama to pregnant rats reverses the depressed adjuvant-induced arthritis of their chronically Trypanosoma cruzi-infected offspring

We demonstrated that administration of interferon gamma (IFN-gama) to the inbred "l" strain of pregnant rats conferred partial resistance on their offspring to challenge with Trypanosoma cruzi. We now examine if this intervention also modifies the reportedly immunodepressed cellular responses which occur during chronic infection. Offspring were born to mothers undergoing one of the following procedures during gestation: subcutaneous injections of recombinant rat IFN-gama, 50,000 IU/rat, five times/week for 3 weeks, which was started on the day of mating (IFN-Mo); infection with 106 trypomastigotes of T. cruzi at 7, 14, and 21 days after mating plus IFN-gama treatment as given to the former group (TcIFN-Mo); the same protocol except that physiological saline was injected instead of IFN-gama (Tc-Mo); injection of physiological saline only (control-Mo). All offspring groups (N = 8-10/group) were infected at weaning and were assessed 90 days later for their adjuvant-induced arthritic response or levels of major T cell subsets in spleen and lymph nodes. TcIFN-Mo and IFN-Mo offspring showed a reestablished arthritic response, which remained within the range seen in controls. Immunolabeling studies on parallel groups of 90-day-infected offspring showed that the inverse CD4/CD8 cell ratio that is usually seen in lymphoid organs from these chronically infected rats (median 0.61) appeared to have recovered in the TcIFN-Mo and IFN-Mo groups (median 1.66 and 1.78, respectively) and was not different from uninfected controls (1.96). These studies indicate that early stimulation with IFN-gama is able to reverse the immunosuppressive state that is usually present during the chronic period of the experimental infection.

Chronic Trypanosoma cruzi infection in the rat: cyclophosphamide-induced recovery of adjuvant arthritis correlates with changes in the levels of lymph node T-lymphocytes and class II+ cells.

We have previously reported that treatment with cyclophosphamide (Cy) reversed the partial resistance of chronically Trypanosoma cruzi-infected rats to adjuvant-induced arthritis (AA) and caused a slight enhancement of arthritis in controls, when given 48 h before induction. To ascertain whether this Cy effect could be associated with regional changes of immunocompetent cells, popliteal lymph nodes were studied for their T-cell subsets and cells carrying class II major histocompatibility (MHC) antigens (1-A and 1-E molecules). Analysis at the time of arthritis induction revealed that infected rats receiving Cy 48 h earlier appeared to have recovered from the inverse balance of major T-cell subsets and showed 1-E+ cells lowered to normal, whereas values from control rats remained unchanged by Cy treatment. Establishment of AA was associated with substantial changes in the phenotype of lymph node cells that drained the affected limb. Changes were equally recorded in control and infected arthritic rats, and consisted of a significant raise of CD4+ and I-A+ cells along with lowered numbers of CD8+ and I-E+ cells. Treatment with Cy lowered even further the levels of CD8+ cells, while causing no affectation in the number of CD4+ cells that remained increased as in the arthritic counterparts receiving no Cy. Comparative analysis of class II MHC+ cells in Cy-treated rats revealed an additional decrease of I-E+ cells in draining lymph nodes from infected and control rats, which coincided with a simultaneous increase in I-A+ cells in the uninfected group. It is suggested that a deletion of a regulatory T-cell subset as well as an improved presentation of arthritogenic peptides may at least underlie the Cy-induced enhancement of the arthritic response.

Acute and chronic experimental Trypanosoma cruzi infection in the rat. Response to systemic treatment with recombinant rat interferon-gamma.

We examined the effects of recombinant rat interferon-gamma (IFN-gamma) injections on the parasitologic, serologic, immunologic and histopathologic features of acute and chronic experimental Trypanosoma cruzi (T. cruzi) infections in "l" rats. Upon infection at weaning, two rat groups were allocated to receive a 20-day cycle of IFN-gamma injections, 20,000 IU/rat each, which started at 1, and 7 days post-infection (pi). Treatment with IFN-gamma, initiated at either 1 or 7 days pi, resulted in comparatively lower peak parasitemias (P < 0.02) but in similar levels of anti-T. cruzi circulating antibodies and serum IFN-gamma activities. The latter appeared significantly increased during acute infection whereas biologically active tumor necrosis factor was virtually undetectable in serum from infected rats regardless of whether they had been given IFN-gamma or not. The prevalence of chronic focal myocarditis in IFN-gamma-treated infected rats showed no differences with respect to the one recorded in control-infected counterparts. The inverse CD4/CD8 ratio of spleen and lymph node T cells that usually accompanies chronic infection was reversed by IFN-gamma. Mononuclear cells carrying class II I-A and I-E molecules, that were found to have increased at both compartments, appeared also modified upon IFN-gamma treatment with an overincrease of I-A-positive cells, and a normalization of I-E-bearing cells.

Effect of aging on autoimmune response to rat male accessory glands: young, but not aged, antigen-presenting cells efficiently induce suppression in aged rats.

The present report analyzes the suppressor cell system of aged rats in an experimental model of autoimmunity to rat male accessory glands (RAG). A state of specific suppression to RAG was induced when young rats are pretreated with peritoneal cells (PC) obtained from syngeneic young rats i.p. injected 2 h previously with chromatographic fraction I (Sephadex G-100) (FI) of RAG (yFI-PC). Although the yFI-PC injection diminished the DTH in aged rats the autoimmune response remained positive. Peritoneal cells obtained from aged rats injected with FI of RAG (oFI-PC) did not suppress the DTH response in either aged or young rats. In both young and aged, pretreatment with yFI-PC stimulates spleen cells capable of inducing suppression (inductor-phase suppressor cells) when they are transferred to young recipients. However, the spleen inductor-phase suppressor cells of 12-month-old rats are unable to suppress the autoimmune response in their own aged environment. To obtain effective suppression in 12-month-old rats, the injection of yFI-PC was necessary prior to and subsequent to immunization. In this work we observe that 12-month-old rats could efficiently induce inducer phase and effector-phase suppressor cells when the adequate young antigen-presenting cells were present to stimulate them.

Effects of thymus supernatants on the phenotype of different subsets of peritoneum antigen-presenting cells.

Peritoneal cells (PC) obtained 2 h subsequent to intraperitoneal (i.p.) injection of low doses (200 micrograms) of a purified fraction of rat male accessory glands (FI-RAG) are phenotypically and functionally different from those obtained 24 h after i.p. injection. In fast, PC obtained 2 h after FI-RAG injection are mainly IE+ and are involved in inducing specific suppression to RAG. In contrast, PC obtained 24 h after FI-RAG injection are mainly IA+ and capable of inducing specific response to RAG. For their induction, IA+ PC require cells within or recently derived from bone marrow. In order to analyze the mechanisms involved in IA+ bone marrow-dependent cell generation in the peritoneum, we studied the distribution of FI-RAG following i.p. injection. It was established that FI-RAG is found mainly in the thymus 2 h after injection and remains there for at least 24 h. Subsequently, we analyzed, in 4 groups of rats, the influence of thymic culture supernatants on the phenotype of cells appearing in the peritoneal cavity 2 h after FI-RAG injection. An increase in IA+ PC was observed 2 h after i.p. injection of FI-RAG in animals that had received either supernatants from normal thymic cells cultured with FI-RAG or those from thymic cells taken from animals injected with FI-RAG 2 h prior to being killed. Supernatants of thymic cells from animals injected with FI-RAG 24 h prior to being killed or from normal thymic cells do not increase the percentage of IA+ PC.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced myocardial lesions in chronically Trypanosoma cruzi-infected rats subjected to adult thymectomy.

Control animals and rats infected 90 days earlier, by inoculation of 1 x 10(6) trypomastigotes of Trypanosoma cruzi at weaning, were subjected to adult thymectomy (ATx) or sham operation (S-ATx) and assessed 3 months later for the presence of myocardial lesions and levels of lymph node and spleen T-cell populations. Chronic focal myocarditis (CFM) developed in 78% and 84% of S-ATx or ATx infected rats, respectively. While the two groups of infected rats did not differ as to the occurrence of myocardial lesions, large foci of CFM were more prevalent in ATx infected rats. Chronic T. cruzi (Tc) infection resulted in decreased CD4+ and increased CD8+ lymph node and spleen cell, with CD8+ lymphocytes being lowered to normal values in the spleen of the ATx infected group. It is suggested that ATx might act by interfering with a down-regulating immunoregulatory mechanism, leading to an exacerbation of autoimmune reactions believed to be involved in the generation of myocardial damage.

[Aortic insufficiency due to quadricuspid aortic valve]. / Insuficiência aórtica por valva aórtica quadricúspide.

In a 45 year old patient with clinic diagnosis of aortic regurgitation the two-dimensional echocardiography demonstrated a quadricuspid aortic valve and severe aortic regurgitation by Doppler. The quadricuspid aortic valve is a rare pathology, usually not associated with other cardiovascular pathologies and in which there is evolution with aortic regurgitation due to malposition of the four cusps.

Effect of gangliosides in the autoimmune response induced by liposome-associated antigens.

A model of autoimmunity to rat male accessory glands (RAG) was recently developed by intraperitoneal administration of three doses of native RAG associated with liposomes. In this work we analysed the effects of gangliosides in the cellular response to RAG when they were intraperitoneally administrated prior to the second dose of liposome-associated RAG. Results show that the ganglioside treatment could modify an established DTH response. Also, gangliosides markedly reduced the number of Ia antigen-positive peritoneal exudated cells (PEC). However, they modified neither the processing of liposomes through PEC nor their viability. Moreover, we obtained cellular response by transferring PEC from immunized donors into naive receptors.

Antigen-induced inhibition of the autoimmune response to rat male accessory glands: bone marrow dependence of the enhancement of IA+ but not IE+ antigen-presenting cells.

IE+ peritoneal cells (PC), involved in the induction of suppression of autoimmune response to rat male accessory glands (RAG), are obtained from rats 2 h after i.p. injection of a purified fraction (FI) of RAG (FI-PC2h). In contrast, IA+ PC, involved in the induction of autoimmune response to RAG, are obtained from rats 24 h after FI of RAG injection (FI-PC24h). The present report analyzes the effect of irradiation or irradiation/bone marrow reconstitution on the induction of both populations of PC. Peritoneal cell donor rats were irradiated in a telegamma therapeutic Cs137. Twenty hours later half of them were i.v. reconstituted with 40 x 10(7) bone marrow cells. Six days later rats were i.p. injected with 200 micrograms of FI of RAG and 10(7) resident PC. The PC were harvested 2 h or 24 h later. The ability of resident PC to yield IE+ FI-PC2h involved in the induction of suppression is not impaired by irradiation, but the ability of resident PC to yield IA+ FI-PC24h involved in the induction of a positive response is impaired by irradiation and restored by bone marrow reconstitution of irradiated rats. Culture of normal PC with FI of RAG for 2 h or 24 h shows a selective increase in IE+ cells able to induce suppression to RAG.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of aging on the autoimmune response to rat male accessory glands: deficit of I-E-positive peritoneal cells capable of inducing suppression.

The present report analyzes the ability to induce suppression to rat male accessory gland (RAG) autoantigens and the characteristics of T suppressor (Ts)-inducer peritoneal cells (PC) in old rats which show increased autoimmune responses. The injection of young rats with a purified fraction (FI) of RAG 10 and 3 days prior to immunization with chemically modified RAG (MRAG) markedly reduced the immune response to RAG autoantigens when compared with young rats which had only been immunized (controls), while the pretreatment of old rats did not block the delayed-type hypersensitivity reaction to MRAG when compared with control old rats. The study of cell surface markers on PC from rats injected i.p. 2 h previously with FI of RAG (FI-PC) showed an increase of OX-6 (I-A) and a decrease of OX-17 (I-E) in FI-PC of old rats with respect to FI-PC of young animals, which showed a selective increase of I-E+ Ts-inducer PC. The i.p. injection of FI-PC from old rats into young recipients, 10 and 3 days prior to immunization with MRAG in complete Freund's adjuvant, did not modify the autoimmune response when compared with controls. By contrast, the injection of young and old rats with FI-PC from young animals induced a significant suppression of the autoimmune response. The reduced percentage of I-E+ suppressor-inducer PC provides an explanation for the diminished ability to induce suppression to RAG autoantigens in old rats.

Antigen-induced inhibition of autoimmune response to rat male accessory glands: distinct characteristics of I-A- and I-E-positive peritoneal cells.

The present report describes different aspects of two populations of peritoneal cells (PC) obtained from rats injected i.p. 2 h or 24 h previously with a suppressor dose of a purified fraction (FI) of rat male accessory glands (RAG) (FI-PC2h and FI-PC24h, respectively). The FI-PC2h, which are mainly I-E (OX17) positive and can suppress the autoimmune response to RAG autoantigens, have an elevated phagocytic activity against Candida albicans and capacity to reduce the dye nitroblue tetrazolium. In contrast, FI-PC24h, which are mainly I-A (OX6) positive and can potentiate the autoimmunity to RAG autoantigens, have a diminished capacity to reduce the dye and a diminished phagocytic activity. Moreover, the Toxoplasma gondii appear to have a different effect on both populations. The parasites can invade FI-PC2h while FI-PC24h offer resistance to T. gondii aggression. FI-PC2h cultured during 22 h (FI-PC2-24h in vitro), or PC obtained from syngeneic recipients injected i.p. 22 h previously with FI-PC2h (FI-PC2-24h in vivo) show, as FI-PC2h, an increase of the I-E+ cells and capacity to induce suppression of the delayed-type hypersensitivity response to RAG autoantigens when they are injected to syngeneic rats 10 and 3 days prior to the immunization with chemically modified (diazotized arsanilic and sulfanilic acid) RAG in complete Freund's adjuvant. The PC obtained 24 h after injection of irradiated rats with N-PC plus FI show an increase of I-E+ cells whereas an enhancement of I-A+ cells can be observed when the PC are obtained 24 h after injection of irradiated and bone marrow-reconstituted rats with N-PC plus FI. These findings appear to indicate that FI-PC2h and FI-PC24h are functionally different and that the population obtained 24 h after injection of FI of RAG could not originate from either the population present 2 h after injection of FI of RAG injection nor from normal PC. They appear to require bone marrow precursors.

Antigen induced inhibition of autoimmune response to rat male accessory glands: role of thymocytes on the efferent phase of the suppression.

In the present study, we report that Cy-sensitive, MRAG-adherent spleen mononuclear (SpM) inductor-phase T suppressor (Ts) cells obtained from rats pretreated with low doses of a purified fraction (FI) of rat male accessory gland antigens (RAG) are mainly OX19+ and W3/25+. Furthermore, thymocytes from rats pretreated with FI of RAG restore the suppression of the autoimmune response to RAG autoantigens in irradiated recipients of SpM inductor-phase Ts cells. In contrast, thymocytes from rats pretreated with rat heart saline extract (unrelated antigen) did not recuperate the suppression of the autoimmune response detected by macrophage migration inhibitory factor (MIF) and delayed-type hypersensitivity. The suppressor thymocytes did not directly exert their inhibitory effect because they were not effective to suppress the autoimmune response to RAG autoantigens when irradiated recipients did not receive SpM inductor-phase Ts cells. The effect of these thymocytes was found in PNA--but not in PNA+ thymic cell population. The perithymic injection of Toxoplasma gondii did block their suppressor activity. The present report clearly shows an active participation of thymus in the efferent phase of the suppressor circuit that controls the autoimmune response to MRAG. The implications of these findings are discussed.

Antigen-induced inhibition of autoimmune response to rat male accessory glands: distinct role of I-A and I-E-positive peritoneal cells.

The present report describes the structural and functional characteristics of the population of peritoneal cells (PC) from rats injected intraperitoneally (i.p.) 2 h or 24 h previously with a suppressor dose of a purified fraction (FI) of rat male accessory glands (RAG: FI-PC2h and FI-PC24h, respectively). Both populations of PC showed the presence of the autoantigens of RAG on their membrane. The study of cell surface marker showed increase of OX17 (I-E) in FI-PC2h and OX6 (I-A) in FI-PC24h. I.p. injection of FI-PC2h 10 and 3 days prior to immunization with chemically modified (diazotized arsanilic and sulfanilic acid) RAG (MRAG) in complete Freund's adjuvant induced suppression of the delayed-type hypersensitivity (DTH) response to MRAG, whereas the i.p. injection of FI-PC24h induced potentiation of DTH response to MRAG when compared with controls (animals injected 10 and 3 days prior to immunization with PC from rats injected i.p. with an unrelated antigen). The treatment of FI-PC2h with OX17 and FI-PC24h with OX6 prior to the transfer blocked the suppression and potentiation described above. These findings show that the i.p. injection of an FI of RAG at a suppressor dose induces PC with immunologically opposite characteristics, depending on the time of obtention.

Potentiation of autoimmune response in rats infected with Toxoplasma gondii. Inhibition of suppressor system and impairment of thymic cellular populations.

In the present work we studied the influence that an infection with Toxoplasma gondii in thymus proximity produces on the suppression of autoimmune response to autoantigen of rat male accessory glands (RAG). The suppression was achieved injecting syngeneic animals with low doses of autoantigen of RAG previous to the immunization with chemically modified rat male accessory glands (MRAG). Rats were infected in thymus proximity with 3 x 10(3) trophozoites of T. gondii before or after to be suppressed. Controls were rats only infected or only suppressed. The delayed hypersensitivity response against MRAG, (DTH test), was significantly potentiated in rats only infected and in the animals suppressed before the infection (p less than 0.001). The suppression was not inhibited in the animals suppressed after infection. The suppression of humoral response against MRAG studied by ELISA and passive hemagglutination test was prevented in rats infected before as well as in rats infected after the induction of suppression (p less than 0.001). Decrease of CD4+ CD8+ and Ox18+ (class I MHC antigen) and increase of CD4+ CD8- and CD4- CD8- thymocytes was observed in the rats where the DTH response was potentiated. These results indicate that the infection with T. gondii in thymus proximity was able to inhibit the suppression of response to autoantigen of RAG producing selective impairment in thymic suppressor influence.

Specific neonatally-induced tolerance to rat male accessory glands antigens. Transference of specific suppression by spleen mononuclear cells.

The immune response of infant rats was studied following (1) immunization of their mothers with modified rat male accessory glands (MRAG) emulsified in complete Freund's adjuvant (CFA), (5 mg/ml or 25 mg/ml) or with human serum albumin (HSA), (5 mg/ml or 25 mg/ml) and (2) intradermal immunization of the offspring at 21 days of age with 5 mg of MRAG-CFA and 5 mg of HSA-CFA. Antibodies to MRAG or to HSA were observed in the sera obtained 20 days after the birth of the offspring. Delayed hypersensitivity (DTH) against MRAG studied 13 days after immunization was significantly reduced in the male offspring born to mothers immunized with 5 mg of MRAG-CFA compared with that of males born to mothers immunized with the same dose of HSA-CFA (P less than 0.0005). In contrast, when 25 mg of MRAG-CFA were used to immunize the mothers, the lack of DTH response to MRAG was observed in male and female offspring (P less than 0.0005 for both groups). In all cases, the DTH response to HSA was positive. The spleen mononuclear (SpM) cells transferred from rats unresponsive to MRAG to normal rats 24 h before the immunization with MRAG-CFA and HSA-CFA did not suppress the immune response whereas transference of SpM cells from suppressed animals to animals previously immunized depressed the DTH response to MRAG (suppression of the expression). The response to HSA was not affected. We can conclude that the suppression is antigen specific.

[Regulation of the autoimmune response against antigens of male accessory glands of rats]. / Estudio de la regulación de la respuesta autoinmune contra antígenos de glándulas sexuales accesorias masculinas de rata.

Rats immunized with chemically modified rat male accessory glands (MRAG) elicit organ and species specific autoimmune response. We have developed suppression of autoimmunity to MRAG injecting syngeneic rats, previous to immunization with MRAG-CFA, with low doses of the same antigen. The unresponsiveness was mediated, by inducer phase, cyclophosphamide (Cy)-sensitive, antigen specific, T suppressor lymphocytes and effector phase, Cy and irradiation sensitive T lymphocytes. Moreover, we demonstrated that macrophages could play a role in the induction of these MRAG-specific suppressor T lymphocytes. On the other hand, we studied the influence of an infection with Toxoplasma gondii on rats immunized with MRAG-CFA. The cellular and humoral immune responses to MRAG were selectively potentiated in animals infected in thymus proximity, whereas the infection did not modify the response to an heteroantigen, human serum albumin (HSA). The i.p. infection did not alter the cellular response. The potentiation of cellular autoimmune response was correlated with thymic involution and proliferation of lymphocytes and plasma cells. A decrease of Ox-8, Ox-18 and Ox-17 surface markers in thymic cellular population and an increase of immature thymocytes (PNA+) were observed in these animals in correlation with the blockage of the effector phase of suppressor cell circuit. In another study we found that the male kits born to mothers immunized with 5 mg of MRAG-CFA showed significantly reduced DTH response to MRAG. When the mothers were immunized with 25 mg of MRAG-CFA the lack of DTH response was observed in male and female kits. In all cases, the DTH response to HSA was positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-induced inhibition of autoimmune response to rat male accessory glands. Role of macrophages in the induction of suppressor cells.

The present paper describes a mechanism responsible for the induction of inducer-phase suppressor cells effective to suppress the autoimmune response to rat male accessory glands (RAG). In fact, we reported here that marked suppression of delayed type hypersensitivity (DTH) reaction and humoral response to chemically modified rat male accessory glands (MRAG) can be obtained when previously to be immunized with MRAG in complete Freund's adjuvant (CFA) syngeneic rats were pretreated with peritoneal cells (PC) coupled with a purified fraction of RAG (containing the autoantigen). The involvement of MRAG-specific inducer-phase suppressor cells was demonstrated by adoptive transfer experiments of spleen mononuclear cells from unresponsive donors to normal syngeneic rats 24 h prior to immunization of the recipients with MRAG-CFA. The PC used to treat the animals show a large proportion of non-specific-esterase positive, Ox-41 bearing macrophage-like cells. Moreover, the antigen-coupled PC able to trigger the suppressor cells showed the presence of the autoantigen of RAG on their surface. The role of the antigen presenting cells in the induction of MRAG-specific inducer-phase suppressor cells is discussed.

Estudio de la regulación de la respuesta autoinmune contra antígenos de glándulas sexuales accesorias masculinas de rata. / [Regulation of the autoimmune response against antigens of male accessory glands of rats]

Rats immunized with chemically modified rat male accessory glands (MRAG) elicit organ and species specific autoimmune response. We have developed suppression of autoimmunity to MRAG injecting syngeneic rats, previous to immunization with MRAG-CFA, with low doses of the same antigen. The unresponsiveness was mediated, by inducer phase, cyclophosphamide (Cy)-sensitive, antigen specific, T suppressor lymphocytes and effector phase, Cy and irradiation sensitive T lymphocytes. Moreover, we demonstrated that macrophages could play a role in the induction of these MRAG-specific suppressor T lymphocytes. On the other hand, we studied the influence of an infection with Toxoplasma gondii on rats immunized with MRAG-CFA. The cellular and humoral immune responses to MRAG were selectively potentiated in animals infected in thymus proximity, whereas the infection did not modify the response to an heteroantigen, human serum albumin (HSA). The i.p. infection did not alter the cellular response. The potentiation of cellular autoimmune response was correlated with thymic involution and proliferation of lymphocytes and plasma cells. A decrease of Ox-8, Ox-18 and Ox-17 surface markers in thymic cellular population and an increase of immature thymocytes (PNA+) were observed in these animals in correlation with the blockage of the effector phase of suppressor cell circuit. In another study we found that the male kits born to mothers immunized with 5 mg of MRAG-CFA showed significantly reduced DTH response to MRAG. When the mothers were immunized with 25 mg of MRAG-CFA the lack of DTH response was observed in male and female kits. In all cases, the DTH response to HSA was positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Delayed hypersensitivity and lesions following isoimmunization with modified rat male accessory glands: kinetics of induction.

The kinetics of the cellular immune response to rat male accessory glands were studied in Wistar rats isoimmunized with modified rat male accessory glands extract and complete Freund's adjuvant at 0, 30 and 45 days. The animals were divided into seven groups, and each group was sacrificed weekly. One immunization was sufficient for the induction of 2-, 6- and 24-h footpad reactivity. The reaction increased until 21 days post-immunization. After the second injection the reaction decreased and was negative 12 days later. Migration inhibitory factor (MIF) activity monitored by a mixed-direct assay was demonstrated in rats from all groups except in the animals studied at day 42 in which macrophage migration was markedly stimulated. The absence of MIF activity correlated with a lack of delayed type hypersensitivity (DTH) response. The humoral response was studied and detected by passive hemagglutination in a few sera after the first immunization. A second injection was necessary to obtain a more frequent occurrence and higher titres of antibodies. Histological modifications in the target organs started to appear in the group of animals studied at 35 days and were characterized by a mononuclear infiltrate in the prostate, coagulating glands and seminal vesicles. In several cases there was also infiltration of polymorphonuclear cells. Specimens obtained at 35 days showed the most severe lesions.