NKT cells in the rat: organ-specific distribution of NK T cells expressing distinct V alpha 14 chains.

Rat invariant TCR alpha-chains and NKT cells were investigated to clarify whether CD1d-mediated recognition by NKT cells is conserved further in evolution. Rats had multiple-copies of TRAV14 genes, which can be categorized into two types according to the diversity accumulated in the CDR2 region. Rats retained invariant TCR alpha forms with the homogeneous junctional region similar to mouse invariant TRAV14-J281. The proportion of invariant TCR among V alpha 14+ clones was 12.9% in the thymus and increased in the periphery, 31% in the spleen and 95% in hepatic sinusoidal cells. The invariant TRAV14-J281 was expressed by liver sinusoidal and splenic NKT cells with CD8, CD44high, and TCR V beta 8. Type 1 invariant TCR alpha was expressed more frequently in hepatic lymphocytes, while type 2 invariant TCR alpha was expressed predominantly in the spleen. Both types of cells cytolyzed to and were stimulated to proliferate by CD1d-expressing cells in a CD1d-restricted manner. These results suggested that rat NKT cells bearing distinct V alpha 14 chains are distributed in a tissue-specific pattern. NKT cell populations in rats were more variable than those in mice, indicating that they play novel roles in nature. The implication of the molecular interaction between the structurally diverse invariant TCR alpha and CD1d/ligand complex in different organs is discussed.

Structural organization of rat CD1 typifies evolutionarily conserved CD1D class genes.

The non-major histocompatibility complex (MHC)-encoded CD1 family has recently emerged as a new antigen-presenting system that is distinct from either MHC class I or class II molecules. In the present study, we determined the genomic structure of the rat CD1 locus. It was extremely similar to mouse CD1 genes, especially to CD1D1. The 5' flanking region of the CD1 gene contained the binding motifs for two cytokine-inducible transcription factors, NF-IL2-A and NF-IL6. Some regulatory elements found in MHC class I genes (enhancer A, enhancer B, and the IFN response element) were absent. It is of interest that a tyrosine-based motif for endosomal localization found in the human CD1b cytoplasmic tail was encoded by a single short exon which was conserved in all CD1 molecules except for CD1a. Southern blot and direct sequencing analyses of inbred rat strains suggested very limited polymorphism in the 5' region where a hydrophobic ligand-binding groove is encoded; a single base substitution resulted in amino acid alteration of alanine (GCT) to valine (GTT) at codon 119. Comparison of the overall exon-intron organization of CD1 genes revealed that the length of the intron was also characteristic to each of the two classes of CD1 genes, classic CD1 and CD1D; such categorization has hitherto been made according to the sequence similarity of the coding region. This finding provides further support for the hypothesis that the two classes have different evolutionary histories. In contrast to the complete absence of the classic CD1 in rats and mice, the entire region of nonpolymorphic CD1D has been conserved through mammalian evolution. Similar functional properties of rodent CD1 and human CD1d are implied.

Polymyositis associated with thymoma and the subsequent development of pure red cell aplasia.

A 53-year-old woman with polymyositis associated with thymoma subsequently developed pure red cell aplasia (PRCA). She was hospitalized because of fever and muscle weakness, and diagnosed as having polymyositis by muscle biopsy. Remarkable clinical improvement followed administration of prednisolone. Progressive anemia became evident, however, while prednisolone was being tapered. Erythroid aplasia and the presence of thymoma confirmed the diagnosis of PRCA. Further examinations revealed that cytotoxic T cells may play an important role in the pathogenesis of this case.

Collagenous colitis.

Collagenous colitis is characterized clinically by chronic watery diarrhea and pathologically by colonic mucosal subepithelial collagen deposition. We report a 72-year-old woman who had collagenous colitis associated with chronic watery diarrhea. She received a non-steroidal anti-inflammatory agent (sulindac) because of rheumatoid arthritis. Histological examination of biopsy showed a thick subepithelial collagen layer with lymphocytes, plasma cells, and infiltration of a few eosinocytes in the lamina propria. These findings led to the diagnosis of collagenous colitis. After treatment with salazosulfapyridine, her bowel movement became normalized and mucosal subepithelial collagen deposition disappeared.

Development of transient thyroid disease and reaction during treatment of chronic hepatitis C with interferon.

Six of 50 (12%) patients with chronic hepatitis C who were treated with interferon developed thyroid disease or an autoimmune thyroid reaction while undergoing treatment. One patient developed silent thyroiditis, with an increase in serum triiodothyronine (T3), thyroxine (T4), free T3, free T4, and markedly suppressed thyroid-stimulating hormone (TSH) levels, accompanied by the appearance of both antithyroglobulin (TgAb) and antimicrosomal antibodies (McAb). One patient developed hypothyroidism in association with moderately elevated TSH levels and high titers of McAb. TSH, TgAb, and McAb levels returned to the initial values at least 4 months after the end of interferon treatment (9 months of follow up). Four patients whose TgAb and/or McAb levels were elevated during treatment with interferon had been diagnosed as having subclinical autoimmune thyroiditis; however, their thyroid function remained in the normal range. These results suggested that treatment with interferon can cause a transient autoimmune thyroid reaction and disease as a side effect.

Histological findings in asymptomatic hepatitis C virus carriers.

There is controversy about clinical management of individuals who persistently have hepatitis C virus antibodies (HCVAb) but who have no symptoms or signs of liver disease. Liver biopsy samples were taken from 15 individuals, all of whom had normal alanine aminotransferase (ALT) levels, to determine the prevalence of liver disease and whether HCVAb and HCV-RNA correlate with histological findings. Eleven patients with hepatitis C viremia had histological evidence of chronic hepatitis on biopsy. On the other hand, four HCV-RNA-negative individuals had almost normal liver histology. These findings indicate that serum HCV-RNA is a sensitive and specific marker of liver disease in HCVAb-positive subjects, independent of ALT levels. Furthermore, these results suggest that there are very few histologically healthy carriers of HCV among HCV-RNA-positive individuals.

An episode of silent thyroiditis in a patient with chronic thyroiditis and papillary adenocarcinoma following alpha interferon treatment for hepatitis C.

In the present paper we described the first case report of silent thyroiditis following alpha-interferon (IFN-alpha) treatment for chronic type C hepatitis in Japan. A 51-year-old woman with chronic type C hepatitis was treated with 6 million units of IFN-alpha three times a week for 24 weeks. Thyroid function was within normal limits and thyroid autoantibodies were negative before IFN therapy. Sixteen weeks after initiation of the treatment, she complained of increasing fatigue, palpitation and losing 7 kg in weight. Thyroid function tests at that time revealed an increase in serum T3, T4, free T3 and free T4 and a markedly suppressed TSH concentration. Both antithyroglobulin antibody (TgAb) and antimicrosomal antibody (McAb) were positive in a dilution of 1: 400. The computed tomographic (CT) scan of the thyroid showed a decrease in the CT number (Hounsfield unit; H.U.) to 58 H.U. (normal, 95-167 H.U.). The 24-h thyroid uptake of 123I was 0.75%. Aspiration biopsy specimens from a nodule in the right lobe and the remaining struma disclosed papillary adenocarcinoma and Hashimoto thyroiditis, respectively. Thyroid function spontaneously returned to normal two months after the onset of thyrotoxicosis through the subclinical hypothyroid stage. After recovery of thyroid function, patient had an operation of papillary cancer without any complications. These clinical features and laboratory findings led to the diagnosis of silent thyroiditis developing in the course of the long-term IFN therapy, which, to our knowledge, has not been reported before in Japan.

Adult T-cell leukemia/lymphoma (lymphoma type) with remarkable gastric lesions: a case report.

We report a case of a 53-year-old woman with adult T-cell leukemia/lymphoma (ATL) (lymphoma type) with multiple gastric lesions, admitted to our hospital because of systemic lymphadenopathy and epigastralgia. Gastroscopy showed a variety of gastric lesions including thickened folds, ulcerations and polypoid lesions. Biopsy specimens obtained from the stomach and lymph nodes revealed diffuse infiltration of pleomorphic mononuclear cells and the integration of HTLV-1 proviral DNA. We demonstrated through the investigation of 30 previously reported cases of ATL that this is a rare case of the lymphoma type of ATL presenting remarkable gastric lesions.