Atrophy of the thymus is one of the consequences of severe insulin deficiency. We describe here that the weight and the architecture of the thymus of diabetic rats is restored towards normal not only by insulin but also by insulin-like growth factor I (IGF-I) treatment. In contrast to insulin, this effect of IGF-I occurs despite persisting hyperglycemia and adrenal hyperplasia. We also investigated the in vivo effect of IGF-I on replication and differentiation of thymocytes from streptozotocin-induced diabetic rats. Thymocytes from diabetic rats incorporated less [3H]thymidine than did thymocytes from healthy rats. Insulin, as well as IGF-I treatment of diabetic rats increased [3H]thymidine incorporation by thymocytes. Flow cytometry of thymocytes labeled with monoclonal antibodies revealed a decreased expression of the Thy-i antigen in diabetic rats compared with control rats. In addition, a major deficiency of thymocytes expressing simultaneously the W3/25 and the Ox8 antigens (corresponding to immature human CD44/CD8+ thymocytes) was observed. These changes were restored towards normal by insulin as well as by IGF-I treatment. The antibody response to a T cell-dependent antigen (bovine serum albumin) was comparable in normal and diabetic rats. We conclude that IGF-I has important effects on the thymocyte number and the presence of CD4+/CD8+ immature cells in the thymus of diabetic rats despite persisting hyperglycemia. However, helper T-cell function for antibody production appears to be preserved even in the severely diabetic state.Insulin deficiency in humans is accompanied by an increased susceptibility to bacterial and mycotic infections. The reason for this is not clear, and results from different studies are inconsistent (for review, see ref. 1). Many of the immunological abnormalities are also observed in experimental diabetes in mice or rats. In streptozotocin-induced diabetic rats, the cellularity of lymphoid organs is diminished; T-cell responses (allograft reactivity and delayed T-cell hypersensitivity), B-cell responses (humoral antibodies), and phagocytic activities have been reported to be impaired (2-5). Insulin administration restores the immune response of diabetic rats toward normal. In hypophysectomized rats, depressed T-and B-cell functions as well as impaired nonspecific immune responses have been reported (6).Hypophysectomized and diabetic rats have decreased insulin-like growth factor I (IGF-I) levels in common and, therefore, may be used to study the effects of IGF-I in vivo.In both models, low levels of IGF-I are accompanied by growth arrest (7,8). The thymus and spleen are smaller and weigh less than in healthy rats of identical body weight (4, 6). IGF-I treatment of hypophysectomized rats and of diabetic rats leads to an increase in body weight and longitudinal bone growth and increases the cell number in primary and secondary lymphatic organs (9).In addition to insulin deficiency, untreated diabetic rats have decreased growth hormone (GH) serum levels and GH receptor number...

Some twenty cases of dispermic chimeras with the karyotype 46,XX/46,XY, discovered because of gonadal dysplasias or a true hermaphroditism, have been reported. This is a report of a phenotypically normal man with 46,XX/46,XY chimerism in whom a prepubertal finding of positive X-chromatin was interpreted as Klinefelter syndrome. The diagnosis was revised 11 years later when the family doctor, who doubted the earlier diagnosis because of the patient's normal-sized testes, sent him to an outpatient clinic. The young man was 23 years old, athletic (74kg, 180cm), with normal body proportions, normal sexual hair distribution, normal libido and potency, normal endocrine parameters, and a normal spermiogram. The karyotype revealed an XX/XY mosaic in a proportion of 1:2. An identical set of maternal markers (Q- and C-banding) was present in male and female cells. Differences were found with respect to two paternal markers. Furthermore, blood, serum, and red cell enzyme groups in five systems showed two phenotypes, again with duality of paternal origin. It is concluded that a positive X-chromatin in prepuperty, especially in the absence of supporting clinical features, must be followed by a karyotype study.