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Gut mucosal immunity to tissue transglutaminase in untreated celiac disease and other gastrointestinal disorders.

Tissue transglutaminase antibodies have not previously been measured in gut secretions. IgA anti-tissue transglutaminase and anti-endomysium antibodies were measured in paired serum and whole gut lavage fluid samples from patients with untreated celiac disease (N = 36), other gastrointestinal diseases (N = 235), and healthy volunteers (N = 13). HLA DQ2 typing was performed in the celiac patients. Whole gut lavage IgA anti-tissue transglutaminase antibody concentrations were raised in 83% of celiac patients, 4% of disease controls, and 8% of volunteers, and the antibody concentrations were significantly higher in celiac patients than in controls (P < 0.0001). Whole gut lavage IgA anti-endomysium antibodies were positive in 67% of celiac patients, but in none of the controls. Whole gut lavage, but not serum, IgA anti-tissue transglutaminase antibody concentrations were significantly higher in DQ2 positive than negative celiac patients. In conclusion, whole gut lavage IgA anti-tissue transglutaminase antibody concentrations are higher in untreated celiac disease than in other gastrointestinal diseases.

Adolescent↗

Protective mucosal immunity elicited by targeted iliac lymph node immunization with a subunit SIV envelope and core vaccine in macaques.

Prevention of sexually transmitted HIV infection was investigated in macaques by immunization with a recombinant SIV (simian immunodeficiency virus) envelope gp 120 and core p27 vaccine. In two independent series of experiments, we used the novel targeted iliac lymph node (TILN) route of immunization, aiming close to the iliac lymph nodes draining the genitorectal mucosa. Rectal challenge with the SIVmac 32H J5 molecular clone in two series induced total protection in four out of seven macaques immunized by TILN, compared with infection in 13 of 14 unimmunized macaques or immunized by other routes (P = 0.025). The remaining three macaques showed either a decrease in viral load ( > 90%) or transient viremia, indicating that all seven TILN-immunized macaques showed total or partial protection (P = 0.001). Protection was associated with significant increase in the iliac lymph nodes of IgA antibody-secreting cells to p27 (P < 0.02), CD8-suppressor factor (P < 0.01), and the chemokines RANTES and MIP-1 beta (P < 0.01).

Animals↗

Humoral and mucosal immunity in infants induced by three sequential inactivated poliovirus vaccine-live attenuated oral poliovirus vaccine immunization schedules. Baltimore Area Polio Vaccine Study Group.

The relative immunity induced by sequential administration of inactivated poliovirus vaccine (IPV) produced in human diploid cells and live attenuated oral poliovirus vaccine (OPV) was evaluated by randomization of 510 infants to receive IPV and OPV sequentially according to one of three experimental schedules, IPV only, or OPV only. The antibody response to two IPV doses was lower than expected. However, for each of the IPV-OPV sequential schedules, the first OPV dose significantly enhanced seroconversion rates and geometric mean microneutralization antibody titers. Three months after the final dose, 96%-99%, 99%-100%, and 81%-100% of infants had antibodies to poliovirus types 1, 2, and 3, respectively, and subjects with two or more prior OPV doses were significantly less likely than those with none or one prior OPV dose to excrete virus in feces after an OPV challenge. Sequential IPV-OPV immunization is now recommended for routine use in the United States. The optimal schedule consists of two IPV doses followed by two OPV doses.

Antibodies, Viral↗

Phenotypical and functional alterations in the mucosal immune system of CD45 exon 9 KO mice.

The protein tyrosine phosphatase CD45 has been shown to be an important regulator of antigen-receptor signaling in both T and B lymphocytes. Lymphocyte populations within the gut mucosa are phenotypically and ontogenetically different from those generally found in secondary lymphoid tissue. In T lymphopenic mice, extrathymic T cell development takes place within the gut. Here we report the characterization of T and B cell populations in the distinct compartments of the gut mucosa and gut-associated lymphoid tissue of CD45-null mice. These data suggest that CD45 is required for the development of the specialized T cell populations within the gut environment as has been previously shown for thymic development. We demonstrate that within the large intestine intraepithelial compartment alphabeta-TCR+ CD4+ T cells are selectively retained by CD45KO mice. T cells and NK cells within the intraepithelium and the gut mucosa associated lymphoid tissue of CD45KO mice frequently possess an activated phenotype, differentiated to produce typical TH1 and TH2 cytokines. These data demonstrate that local environmental differences within the gut can, at least in part, overcome the requirement for CD45 during activation of T cells.

Animals↗

Enhanced mucosal immunity against Eimeria acervulina in broilers fed a Lactobacillus-based probiotic.

The effect of feeding a Lactobacillus-based probiotic on intestinal intraepithelial lymphocyte (IEL) subpopulations and subsequent protection against coccidiosis was investigated in broiler chickens. Day-old male broilers were fed standard rations without control (CONT) or with a commercial probiotic (PROB) Primalac. Differences in IEL subpopulations were assessed by flow cytometry at 21 d postprobiotic treatment. At 25 d of age, a group of randomly selected birds from each diet was inoculated orally with 10,000 (per bird) sporulated oocysts of Eimeria acervulina and kept on the same diets. Fecal material, sera, and intestinal washes were collected 10 d postchallenge with E. acervulina. Birds on the PROB diet had more IEL expressing the surface markers CD3, CD4, CD8, and alphabetaTCR than those of the CONT diet. The probiotic-fed chickens produced less oocysts (P < 0.0001) compared to the untreated, control group (368 x 10(6) in CONT vs. 89 x 10(6) in PROB). The interferon-gamma levels in both serum and intestinal secretions were not significantly different between the two groups. However, CONT group showed higher antibody levels against a recombinant coccidial antigen in the intestinal secretions than the PROB group. No significant difference was found in serum antibody levels against the same antigen. These results dearly indicate that the probiotic bacteria impacted the local immune response as characterized by altered IEL subpopulations and increased the birds' resistance to E. acervulina as reflected by reduced oocyst shedding.

Animals↗

Successful mucosal immunization of cotton rats in the presence of measles virus-specific antibodies depends on degree of attenuation of vaccine vector and virus dose.

After passive transfer of measles virus (MV)-specific antibodies, vaccine-induced seroconversion and subsequent protection is inhibited in cotton rats (Sigmodon hispidus). In this system, an attenuated, recombinant vesicular stomatitis virus expressing the MV haemagglutinin (VSV-H) was found previously to induce neutralizing antibodies and protection against MV challenge after intranasal (i.n.) immunization. Here it is demonstrated that, after i.n. immunization, VSV-H is found in both lung and brain tissue in the absence of clinical signs. Intratracheal inoculation, which does not lead to infection of the brain, proved that immunization via the lung mucosa is sufficient to protect. To reduce or eliminate infection of the brain after i.n. inoculation, stepwise-attenuated VSV-H mutants with truncated cytoplasmic tails of the G protein were tested in cotton rats. A mutant with 9 aa in the G cytoplasmic tail was found at much lower levels in the brain and was protective in the absence or presence of MV-specific antibodies. A more attenuated mutant containing only 1 aa in its tail was not found in brain tissue after inoculation, but it still induced protective antibody to measles in the absence of MV-specific antibody. However, its ability to induce MV-neutralizing antibodies in the presence of passively transferred MV-specific antibodies and its protective capacity was abolished unless higher-dose immunizations were used. This study demonstrates that a lower degree of attenuation is required to be able to immunize in the presence of MV-specific antibodies.

Administration, Intranasal↗