The effect of immuno-depression due to neonatal thymectomy on infections with trypanosoma cruzi in mice

Schmuñis, Gabriel A.; Cappa, S. M. González; Traversa, Oscar; Janovsky, J.F.

doi:10.1016/0035-9203(71)90190-8

Cited by 42 publications

(23 citation statements)

References 17 publications

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“…In considering this possibility, it should be pointed out that immunization of mice with the schistosome protein paramyosin, also a nonsurface protein, induces protective cell-mediated immunity against challenge with Schistosoma mansoni (11). The suggested involvement of cell-mediated immunity also is consistent with results of other studies which show T cells to be one of the major cell populations involved in providing resistance to T. cruzi (8,10,19). In particular, partial elimination of CD4 ϩ or CD8 ϩ T cells by use of monoclonal antibodies, or use of mice which lack CD4 or CD8 molecules as a result of specific genomic deletions, results in mice which are strikingly susceptible to T. cruzi infections (1,12,13,17,23).…”

Section: Resultssupporting

confidence: 79%

Pure paraflagellar rod protein protects mice against Trypanosoma cruzi infection

Wrightsman¹,

Miller²,

Saborío³

et al. 1995

Parasitology Today

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The paraflagellar rod proteins (PAR) purified from Trypanosoma cruzi epimastigotes were shown to protect mice against an otherwise lethal challenge inoculum of 10 3 bloodstream-form trypomastigotes. The injection route used for immunization was shown to have a marked impact on the development of protective immunity. Mice receiving subcutaneous (s.c.) injections of PAR proteins had reduced bloodstream parasitemias and showed 100% survival following challenge. In contrast, mice immunized via the intraperitoneal (i.p.) route developed parasitemia levels equivalent to those of unimmunized controls and did not survive infection. Western blotting (immunoblotting) demonstrated that sera from both i.p. and s.c. immunized mice reacted specifically with PAR proteins; however, the antibody titer of the i.p. immunized mice was approximately 64-fold greater than that of the s.c. immunized mice, suggesting that the protective response in the s.c. immunized mice is cell mediated rather than humoral.Trypanosoma cruzi is a parasitic hemoflagellate that causes Chagas' disease, a major human health problem in Central and South America (4). Chemotherapeutic agents have limited effectiveness against the disease, and no vaccines are available for disease prevention. Experimental vaccines consisting of attenuated forms of the parasite, crude parasite lysates, partially purified proteins, and synthetic peptides derived from the sequence of a 24-kDa excretory protein (ESA) have been tested in laboratory animals with varying degrees of success (reviewed in references 2, 5, 7, 16, and 22). Several of these studies show that susceptible hosts may be partially protected against death by vaccination prior to challenge; however, individual antigens capable of ensuring survival against an otherwise lethal challenge have yet to be identified.In an attempt to identify and purify protective antigens, we focused on proteins present in the flagellum of T. cruzi. The rationale for this approach is based on studies demonstrating that vaccination with crude flagellar extracts are effective in both inducing protective immunity (i.e., 90% survival) in mice after challenge (15,20,21) and reducing tissue lesions in immunized mice compared with nonimmunized mice following a challenge infection (14). In contrast, immunization with a membrane-enriched fraction from the body of the parasite was less effective in inducing a protective response, suggesting that the protective antigen(s) may be unique to the flagellum. A potential candidate for such antigens is the paraflagellar rod, a prominent structure present only in the flagellum of the parasite (5). We have shown that the paraflagellar rod contains two distinct proteins, PAR 1 and PAR 2, and have determined conditions that allow these proteins to be isolated in amounts and purity sufficient for immunization trials (3,18).In this paper, we report the ability of the purified PAR proteins to induce an immune response in mice capable of protecting against an otherwise lethal inoculum of T. cruzi trypomastigote...

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Section: Resultssupporting

confidence: 79%

Pure paraflagellar rod protein protects mice against Trypanosoma cruzi infection

Wrightsman¹,

Miller²,

Saborío³

et al. 1995

Parasitology Today

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“…shown by experiments showing that neonatal thymectomy (Tx; [13]) as well as the ndnu mutation (with an absence of thymus development [14, 1.51) accelerated the course of the disease. Moreover, very recent results using nude mice as experimental models for infection indicate that thymocytes, but not splenic T cells, are able to induce a strong inflammatory reaction around cardiac muscle cells [16].…”

Section: Introductionmentioning

confidence: 98%

Studies on the thymus in chagas' disease

Savino

Leite-De-Moraes

Hontebeyrie-Joskowicz

et al. 1989

Eur J Immunol

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Previous observations demonstrated severe thymocyte depletion in mice undergoing acute Chagas' disease. These data led us to investigate the status of the thymic microenvironment in these animals. Young adult C57BL/6 and C3H/HeJ mice were infected i.p. with 10(5) blood-derived trypomastigote forms of Trypanosoma cruzi (CL strain) and killed 7-14 days after infection. Sera were then analyzed for thymic hormone (thymulin) levels, and frozen thymus sections were studied by immunohistochemistry for the expression of functional antigens (thymulin and Ia), the distribution of distinct thymic epithelial cell subsets and extracellular matrix components. Infected mice exhibited a transient decrease in thymulin production and those with severe thymic atrophy showed a denser Ia-bearing cellular network. In addition, an abnormal localization of the TR5 and CK18 antigens restricted to the medullary and cortical TEC subsets, respectively, was observed. Furthermore, an increase in the basement membrane proteins was detected within thymic lobules. We suggest that the thymic microenvironment is also affected during T. cruzi infection, extending the concept that the thymus should be regarded as a target in Chagas' disease.

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“…1988), mice lacking CD4 and/or CD8 gene expression (Rottenberg et al . 1995), thymectomized mice (Schmunis et al . 1971) and nude mice (nu/nu) (Da Costa et al .…”

Section: Introductionmentioning

confidence: 99%

Evidence for a perforin‐mediated mechanism controlling cardiac inflammation in Trypanosoma cruzi infection

Henriques-Pons¹,

Oliveira²,

Paiva³

et al. 2002

Int J Experimental Path

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Summary. CD8T lymphocytes are considered an important cell population involved in the control of parasitaemia and mortality after Trypanosoma cruzi infection. However, despite recent developments in this field, the mechanism whereby this control is exerted is still not completely understood. Here we have used perforin knockout (±/±) mice infected with Y strain T. cruzi in order to evaluate specifically the participation of the perforin-based cytotoxic pathway in the destruction of cardiomyocytes, cellular inflammatory infiltration, and control of parasitaemia and mortality. We observed that although parasitaemia was equivalent in perforin (/) and (±/±) groups, survival rate and spontaneous physical performance were significantly lower in the perforin deficient mice. The cardiac inflammatory cell infiltration, mostly composed of CD8 cells, was more evident in perforin (±/±) mice. Ultrastructural and immunofluorescence analysis, as well as plasma creatine kinase activity, revealed cardiomyocyte damage and necrosis, more evident in perforin (±/±) mice. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays performed in heart samples revealed similar and modest levels of apoptosis in both perforin (/) and (±/±) mice. These results indicate that perforin does not play a pivotal role in the control of parasitaemia and direct lysis of cardiomyocytes, but seems to be an important molecule involved in the control of cardiac inflammation and pathology induced by a highly virulent strain of T. cruzi.

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The effect of immuno-depression due to neonatal thymectomy on infections with trypanosoma cruzi in mice

Cited by 42 publications

References 17 publications

Pure paraflagellar rod protein protects mice against Trypanosoma cruzi infection

Pure paraflagellar rod protein protects mice against Trypanosoma cruzi infection

Studies on the thymus in chagas' disease

Evidence for a perforin‐mediated mechanism controlling cardiac inflammation in Trypanosoma cruzi infection

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