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PubMed1992

Involvement of the H+/K(+)-ATPase alpha subunit as a major antigenic protein in autoimmune gastritis induced by neonatal thymectomy in mice.

Autoimmune gastritis develops spontaneously in approximately 60% of BALB/c mice thymectomized neonatally. Histologically and clinically it is similar to the atrophic gastritis associated with pernicious anaemia in humans. Here we identified antigenic protein relating to the pathogenesis of autoimmune gastritis in these mice. All sera from 32 thymectomized mice with gastritis contained autoantibodies to the vesicular fraction prepared from rat gastric parietal cells. Immunoblot analysis revealed all of these to react with a 94-kD protein corresponding in molecular mass with the H+/K(+)-ATPase alpha subunit. Some sera were also reactive with 65-85-kD and/or 60-kD proteins, whose sizes correspond to the H+/K(+)-ATPase beta subunit and intrinsic factor, respectively. The finding that immuno-adsorption with these sera resulted in reduction of H+/K(+)-ATPase activity in the vesicular fraction, supported a conclusion of H+/K(+)-ATPase alpha and/or beta subunits as the antigenic proteins. After immunization of normal syngeneic mice with various doses of gastric parietal cells or their vesicular fraction, all sera from animals demonstrating atrophic gastric mucosa with lymphocyte infiltration reacted with the H+/K(+)-ATPase alpha subunit. No antibodies to other proteins were induced even in mice immunized with higher doses of antigen. We therefore conclude that H+/K(+)-ATPase alpha subunit is important as the target antigen in pathogenesis of autoimmune gastritis in neonatally thymectomized mice, probably due to a high affinity for the MHC molecule.

Adenosine Triphosphatases↗
PubMed2004

The influence of partial or total thymectomy during open heart surgery in infants on the immune function later in life.

Infants undergoing open heart surgery often have all or part of their thymus removed. The activity of the immune system has not been investigated thoroughly in these children, and only shortly after the operation. Therefore, it was decided to investigate the activity of the immune system in more detail in children several years after their operation. Peripheral blood samples from 19 children who had undergone open heart surgery during their first months of life was collected (study group) and from 19 age- and gender-matched children (control group). The activity of the immune system was evaluated by measuring the number of different cell types in peripheral blood, the phenotype of lymphocytes and the response of T cells following in vitro stimulation by mitogen, tetanus toxoid and measles antigen. The study group had significantly lower counts of total lymphocytes, which was reflected in a lower number of T cells but not B cells. Furthermore, the study group had significantly lower proportion of T cells (CD3(+)) and helper T cells (CD4(+)), but not cytotoxic T cells (CD8(+)). The level of neutrophils in peripheral blood was significantly higher in the study group. This may indicate enhanced innate immunity when the acquired immunity is defective. The results indicate a shift to extrathymic T cell maturation, which is less efficient for CD4(+) helper cells than for CD8(+) cytotoxic cells.

Antigens, Viral↗
PubMed2006

Evidence for extrathymic T cell maturation after thymectomy in infancy.

Our previous study showed that children who had been partially or completely thymectomized during heart surgery as infants had lower proportions and numbers of total lymphocytes and reduced proportions of T cells (CD3(+)), helper T cells (CD4(+)) and naive T cells (CD3(+) CD4(+) CD45RA(+)), but normal proportion of cytotoxic T cells (CD8(+)). In this study T lymphocytes from a selected group of eight of these children and age- and gender-matched controls were characterized further using flow cytometry to determine phenotypes of T cells and T cell subsets related to T cell regulation and phenotypes suggestive of extrathymic maturation. Immune function was assessed by measuring autoantibodies and antibodies against vaccines. The study group had significantly lower numbers of all the main subsets of T lymphocytes and the composition was different. Thus, the proportions of lymphocytes with the following phenotypes: CD3(+), CD2(+), CD7(+), CD4(+), CD62L(+), CD4(+) CD62L(+) and CD4(+) CD69(-) were significantly reduced in the study group compared with the control group, but significantly higher proportions were seen of lymphocytes expressing CD8alpha(+) CD8beta(-) and TCRgammadelta(+) CD8alpha(+) CD8beta(-). The absolute number and proportion of CD4(+) CD25(+) cells were reduced but the proportions of the subgroup of naive regulatory T cells (CD4(+) CD25(+) CD62L(+)) and non-activated regulatory T cells (CD4(+) CD25(+) CD69(-)) were not reduced in the thymectomized children. We conclude that the phenotypic characteristics of T lymphocytes of children who have lost their thymus in infancy are indicative of extrathymic maturation. T regulatory cells appear to be less affected than other subsets by the general reduction in T cell numbers.

Adolescent↗