IgA in the horse: cloning of equine polymeric Ig receptor and J chain and characterization of recombinant forms of equine IgA

As in other mammals, immunoglobulin A (IgA) in the horse has a key role in immune defense. To better dissect equine IgA function, we isolated complementary DNA (cDNA) clones for equine J chain and polymeric Ig receptor (pIgR). When coexpressed with equine IgA, equine J chain promoted efficient IgA polymerization. A truncated version of equine pIgR, equivalent to secretory component, bound with nanomolar affinity to recombinant equine and human dimeric IgA but not with monomeric IgA from either species. Searches of the equine genome localized equine J chain and pIgR to chromosomes 3 and 5, respectively, with J chain and pIgR coding sequence distributed across 4 and 11 exons, respectively. Comparisons of transcriptional regulatory sequences suggest that horse and human pIgR expression is controlled through common regulatory mechanisms that are less conserved in rodents. These studies pave the way for full dissection of equine IgA function and open up possibilities for immune-based treatment of equine diseases

A review of the human vs. porcine female genital tract and associated immune system in the perspective of using minipigs as a model of human genital Chlamydia infection

International audienceAbstractSexually transmitted diseases constitute major health issues and their prevention and treatment continue to challenge the health care systems worldwide. Animal models are essential for a deeper understanding of the diseases and the development of safe and protective vaccines. Currently a good predictive non-rodent model is needed for the study of genital chlamydia in women. The pig has become an increasingly popular model for human diseases due to its close similarities to humans. The aim of this review is to compare the porcine and human female genital tract and associated immune system in the perspective of genital Chlamydia infection. The comparison of women and sows has shown that despite some gross anatomical differences, the structures and proportion of layers undergoing cyclic alterations are very similar. Reproductive hormonal cycles are closely related, only showing a slight difference in cycle length and source of luteolysing hormone. The epithelium and functional layers of the endometrium show similar cyclic changes. The immune system in pigs is very similar to that of humans, even though pigs have a higher percentage of CD4+/CD8+ double positive T cells. The genital immune system is also very similar in terms of the cyclic fluctuations in the mucosal antibody levels, but differs slightly regarding immune cell infiltration in the genital mucosa - predominantly due to the influx of neutrophils in the porcine endometrium during estrus. The vaginal flora in Göttingen Minipigs is not dominated by lactobacilli as in humans. The vaginal pH is around 7 in Göttingen Minipigs, compared to the more acidic vaginal pH around 3.5–5 in women. This review reveals important similarities between the human and porcine female reproductive tracts and proposes the pig as an advantageous supplementary model of human genital Chlamydia infection

Antisense inhibition of P210 bcr-abl in chronic myeloid leukemia.

The evidence that the bcr-abl gene product (P210) of the Philadelphia chromosome plays a crucial role in the pathogenesis of chronic myeloid leukemia (CML), and the absence of the bcr-abl fused transcript in non-malignant cells makes this messenger RNA an ideal candidate for antisense strategies in CML. To inhibit the expression of the bcr-abl gene, and to try to eradicate Philadelphia-positive cells, different methods can be used: 1) the introduction into the cells of antisense oligonucleotides, 2) the use of specific ribozymes, or 3) the transduction, using retroviral vectors, of stably integrated sequences coding for antisense RNA. Each of these approaches has potential advantages and drawbacks that are discussed below. Although many data emerge that support the use of anti-bcr-abl antisense molecules in CML, numerous questions remain to be completely answered before the most efficient strategy can be designed, either for in vitro or in vivo purposes.Journal ArticleReviewFLWINinfo:eu-repo/semantics/publishe

Characterization of an anti-idiotypic MoAb bearing an internal image of the receptor-binding epitope of cholera toxin.

A mouse anti-cholera toxin (CT) MoAb, mAb1, specific for the GM1-binding epitope of CT, was used to raise a syngenic anti-idiotypic MoAb, mAb2. Purified mAb2 was specific for mAb1 as shown by latex particle counting immunoassay and ELISA. Several experiments of competition between mAb2 and CT for binding to mAb1 demonstrated that mAb2 bore an internal image of the GM1-binding epitope of CT. Binding of mAb2 to GM1 unambiguously corroborated the mAb1-paratopic specificity of mAb2. Furthermore, mAb2 acted as a CT-surrogate antigen: rabbits injected with mAb2 produced some anti-CT antibodies, Ab3, which resembled mAb1 in specificity as expected. The potential use of this mAb2 as vaccine or as prophylactic agent to prevent CT from binding to its cellular receptor is discussed

An interspecies idiotope associated with the anti-cholera toxin response detected by a monoclonal auto-anti-idiotypic antibody.

We have produced an auto-anti-idiotypic (auto-anti-id) monoclonal antibody (mAb) which reacted with syngenic mouse polyclonal anti-cholera toxin (anti-CT) IgG antibody (Ab) and six/eight different anti-CT IgG mAb, but not with normal mouse BALB/c IgG. The binding of this auto-anti-id mAb on one anti-CT mAb was significantly inhibited by polyclonal anti-CT sera of rats, rabbits and mice. Thus the idiotope on anti-CT Ab recognized by this auto-anti-id mAb was public and expressed in different species. Because of the absence of competition between CT and this auto-anti-id mAb for the binding to the six anti-CT mAb, the anti-id mAb was classified as an Ab2 alpha. The efficiency of this auto-anti-id mAb to induce anti-CT Ab3 was tested with success in rabbits and rats. Auto-anti-id mAb-immunized rats were significantly protected against an intraintestinal CT challenge

Protection of rat intestine against cholera toxin challenge by monoclonal anti-idiotypic antibody immunization via enteral and parenteral routes.

A mouse monoclonal anti-idiotypic (anti-id) immunoglobulin M (IgM) antibody, called MAb2, was raised against a mouse monoclonal anti-cholera toxin (anti-CT) antibody (MAb1). The MAb2 was shown, by competition with CT for MAb1, to bear the internal image of an epitope of CT. MAb2 immunization of rats was performed via the intraperitoneal, intragastric, and intrajejunal routes and compared with immunization of rats with either a control, isotype- and allotype-matched MAb or with CT via the same routes. Both serum IgG and bile IgA anti-CT Ab3's were detected by enzyme-linked immunosorbent assay in anti-id MAb2-immunized rats, although their titers were lower than those in CT-immunized rats. No anti-CT antibodies were detected in sera and bile of rats immunized with the control MAb. When tested for degree of gut protection against a CT challenge, rats immunized with MAb2 by the intrajejunal route showed a rather high degree of protection, which was only slightly lower than that of rats immunized with CT via the same route; all rats but one immunized with the control MAb were unprotected. There was, however, no correlation between serum or bile anti-CT titers and degree of gut protection in MAb2-immunized rats. Their serum anti-CT Ab3's were purified by adsorption and elution from a CT immunosorbent and resembled anti-CT MAb1 in their unique reactivity with MAb2. This constitutes to our knowledge the second report of protection against a pathogen by anti-id immunization via the enteric route