Kiyonori Kuki

Squamous cell carcinoma arising in a Warthin’s tumor

Warthins tumor is a well-defined salivary gland neoplasm consisting of epithelial and lymphoid components. However, malignant transformation is extremely rare. Such a patient who developed squamous cell carcinoma within a Warthins tumor of the parotid gland is described and possible pathogenesis is discussed.

Engraftment of Tonsillar Mononuclear Cells in Human Skin/SCID Mouse Chimera —Validation of a Novel Xenogeneic Transplantation Model for Autoimmune Diseases—

Pustulosis palmaris et plantaris (PPP) has been considered as one of the typical tonsillar focal infections, based on the marked clinical improvement of the skin lesions after tonsillectomy. Despite the accumulation of data showing the clinical efficacy of tonsillectomy for this skin lesion, fundamental etiological and pathophysiological issues have yet to be addressed. One primary obstacle hindering investigators has been the lack of an appropriate animal model for this human skin disorder. In the early stage of PPP, it has been reported that lymphocytes, predominantly CD4+ T lymphocytes, infiltrate the palmar and plantar skins. However, the origin and mechanism of infiltration by these lymphocytes is not clear and there are very few reports on whether tonsillar mononuclear cells react directly with the skin. We have been intrigued by the ability to engraft human cells onto severe combined immunodeficiency (SCID) mice, together with the opportunity for long‐term graft survival and ability to adoptively transfer various human immunocompetent cells. In this review, we addressed the existing deficiencies in our understanding of the relationship between tonsils and PPP by using emerging transplantation technology involving SCID mice.

Functions of tonsils in the mucosal immune system of the upper respiratory tract using a novel animal model, Suncus murinus

Conclusion. The human palatine tonsils and the nasopharyngeal tonsil were considered the defense mechanism against ingested or inhaled foreign pathogens. The current findings suggest that the tubal tonsils possess abilities of active transportation of foreign antigens, and will act as inductive and effector sites in the mucosal immune system. Our results also indicated a significant difference in roles of immune responses among individual tonsillar organs, suggesting functional sub-compartmentalization. Objectives. To address the function of tonsils in inducing local immune responses, we evaluated the antigen uptake of tubal tonsils and the induction of specific immune responses in a small laboratory animal with both tubal and palatine tonsils, i.e. Suncus murinus. Materials and methods. S. murinus were injected with 2×106 CFU of FITC-labeled Staphylococcus aureus via the right tympanic cavity. The distribution of the FITC-labeled S. aureus was examined under a fluorescent microscope. S. murinus were also immunized with 100 µg of ovalbumin (OVA) mixed with 2 µg of cholera toxin (CT) via the right external ear meatus every 2 days for 2 weeks. One week after the final immunization, sera, pairs of tubal and palatine tonsils, and the neck lymph nodes were obtained to evaluate the induction of specific immune responses. Results. The FITC-labeled S. aureus particles were detected in tubal tonsils and also in cervical lymph nodes. Total IgA-producing cells and OVA-specific antibody-producing cells were identified in the immunized tubal tonsils. Trans-external ear meatus immunization of tubal tonsils also evoked systemic antibody responses.

Immunological derangement in tonsils with recurrent infections: A study of co-stimulatory factors on tonsillar B lymphocytes

Palatine tonsils are located on the strategic site at an entrance of both the gastrointestinal tract and airways. The tonsil has a double-sided face, i.e., a bright side as an immune organ for protection against microorganisms from outside and a dark side as an infectious organ such as tonsillitis. Numerous studies have reported that the tonsil has immune functions; however, the mechanism of recurrent bouts of tonsillar infections remains to be addressed. n nIn order to understand the immune mechanism in tonsillar lymphocytes, we examined co-stimulatory factors, CD80 and CD86, on tonsillar lymphocytes, which have been shown to be prerequisite for antigen-specific T cell activation in immune responses. We investigated the expression of CD80 and CD86 on B cells from tonsils with recurrent infections more than four episodes per year (the infectious group), from tonsils with chronic tonsillitis less than three episodes per year. The numbers of CD80- and CD86-postive B cells were significantly lower in the infectious group than in the less-infectious group (p<0.05). In addition, the positivity of CD80 and CD86 was well correlated in the less-infectious group, but markedly deranged in the infectious group. Based on our data, the loss of CD80 and/or CD86 was well associated with the number of episodes of tonsillitis. It is inferred that the loss or derangement of CD80 and CD86 may result in insufficient interactions of T and B cells and lead to vulnerability to recurrent infections. n nFrom the clinical point of view, we investigate the relation between the number of episodes of tonsillitis and age to evaluate the spontaneous resolution. We found the tendency of the episode of tonsillitis decreased with age. We advocate the new indication of tonsillectomy. The index of tonsillitis (IT) is calculated that the episodes of tonsillitis/year multiplies morbidity period (year). By this index, we can decide the treatment policy, i.e., tonsillectomy or conservative treatment expecting spontaneous resolution.

Immunity of tonsil and IgA nephropathy – relationship between IgA nephropathy and tonsillitis

Our study hypothesized that cytokines or chemokines induced in tonsils by infectious stimulations play an important role on the exacerbation of the glomerular injuries in patients with IgA nephropathy (IgAN). Tonsils from six patients with IgAN diagnosed by renal biopsy were studied after getting their written informed consents. Tonsils from six patients with tonsil disorders with non-renal disorders were examined as controls. Tonsillar mononuclear cells (TMCs) were isolated and resuspended with RPMI 1640 with 10% FCS. These cells were incubated for 48 h with staphlococcus enterotoxin-B (SEB) or lipopolysaccaride (LPS). The levels of IL-6, IL-8, IL-12 and MCP-1 in the supernatants were measured by solid-phase enzyme-linked immunosorbent assay (ELISA) kits. The actual cytokine concentrations were calculated by determining the standard curves. The experiments were performed in duplicate, and the mean value was calculated. We found that tonsillar mononuclear cells of IgA nephropathy produced mesangial proliferative chemokines (MCP-1, IL-8) in higher amounts compared to tonsils from non-IgA nephropathy. This result suggests that upper respiratory tract infections such as tonsillitis may be one of the risk factors of the aggravation in patients with IgA nephropathy.

Tonsil—a mysterious organ-novel approaches using human skin/SCID chimera

Abstract The concept that altered antigens in the squamous epithelium of the palatine tonsil may serve as a source of autoantibodies for diseases of the palms and soles, i.e., pustulosis palmaris et plantaris (PPP), has been considered for a long time. To study the role of tonsillar mononuclear cells in the onset of PPP lesion, we developed a xenogeneic transplantation model, human skin/severe combined immunodeficiency (SCID) chimera and reconstituted the chimera with human lymphocytes from PPP patients.