Phenotype and natural killer cell sensitivity of a radiation-induced acute T-cell leukaemia (Roser leukaemia) in PVG rats.

A radiation-induced T-cell leukaemia [Roser leukaemia (RL)] in the rat was conditioned for growth in vitro by repeated in vivo-in vitro passages. This in vitro cell line, termed RL-T, maintained its leukaemia-inducing property when transferred to syngeneic PVG rats. It expresses several T-cell markers and the T-cell alpha/beta receptor-CD3 complex. RL-T, furthermore, expresses major histocompatibility complex (MHC) I antigens, both classical (RT1.A) and nonclassical (RT1.C), which makes it susceptible to killing by alloreactive natural killer cells in vitro.

RT1-U: identification of a novel, active, class Ib alloantigen of the rat MHC.

In common with other mammalian species, the laboratory rat (Rattus norvegicus) expresses MHC class I molecules that have been categorized as either classical (class Ia) or nonclassical (class Ib). This distinction separates the class Ia molecules that play a conventional role in peptide Ag presentation to CD8 T cells from the others, whose function is unconventional or undefined. The class Ia molecules are encoded by the RT1-A region of the rat MHC, while the RT1-C/E/M region encodes up to 60 other class I genes or gene fragments, a number of which are known to be expressed (or to be expressible). Here we report upon novel MHC class Ib genes of the rat that we have expression cloned using new monoclonal alloantibodies and which we term RT1-U. The products detected by these Abs were readily identifiable by two-dimensional analysis of immunoprecipitates and were shown to be distinct from the class Ia products. Cellular studies of these molecules indicate that they function efficiently as targets for cytotoxic killing by appropriately raised polyclonal alloreactive CTL populations. The sequences of these class Ib genes group together in phylogenetic analysis, suggesting a unique locus or family. The combined serological, CTL, and sequence data all indicate that these products are genetically polymorphic.

Adrenaline-induced leucocytosis: recruitment of blood cells from rat spleen, bone marrow and lymphatics.

It is well known that adrenaline causes leucocytosis, but the sources and the mechanisms of this have not been clarified. We investigated the contributions of subpopulations of white blood cells to this leucocytosis and the importance of the spleen, bone marrow and lymphatics in releasing leucocytes into the blood stream following an injection of adrenaline. We studied possible effects of adrenaline on blood flow to the spleen and bone marrow to see if any contribution to leucocytosis from these organs could be perfusion dependent. In intact awake rats, total blood leucocytes increased within 5 min to about 220% of baseline concentration, the increases of lymphocytes and neutrophilic granulocytes being about 250% and 160%, respectively. The T and B lymphocytes and natural killer cells were all mobilized, to about 230% to 250% of baseline concentrations. The leucocytosis was short-lasting, so that the cell concentrations returned to baseline within 25 min after adrenaline injection. The bone marrow, spleen, and efferent lymphatics all contributed substantially to this leucocytosis, since band-nucleated granulocytes increased upon adrenaline injection, and splenectomized or thoracic duct drained rats showed a markedly reduced leucocytosis in response to adrenaline. Supplementary data were obtained with bone marrow depleted (with 89Sr irradiation) rats. The release of leucocytes from these organs was apparently not blood-flow dependent in the control rats since organ perfusion remained unaltered after adrenaline injection. Adrenaline was found to stimulate the release of both mono- and polymorphonuclear cells in the awake rat and the release of leucocytes from the spleen, bone marrow and efferent lymphatics to contribute significantly to the leucocytosis.

Treatment of adults with growth hormone (GH) deficiency with recombinant human GH.

In a double blind, cross-over placebo-controlled trial, we studied the effects of 26 weeks of replacement therapy with recombinant human GH on body composition, metabolic parameters, and well-being in 10 patients with adult-onset GH deficiency (GHD). All patients received appropriate thyroid, adrenal, and gonadal replacement therapy. The dose of recombinant human GH was 0.25-0.5 U/kg.week (0.013-0.026 mg/kg.day) and was administered sc daily at bedtime. One patient was withdrawn from the study because of edema and atrial fibrillation. Body composition was estimated with three independent methods: computed tomography, bioelectric impedance, and total body potassium combined with total body water assessments. The Comprehensive Psychological Rating Scale and the Symptom Check List-90 were used to assess any change in psychopathology. After 26 weeks of treatment, adipose tissue (AT) mass decreased 4.7 kg (P < 0.001). Subcutaneous AT decreased by an average of 13%, whereas visceral AT was reduced by 30%. Muscle volume increased by 2.5 kg (5%; P < 0.05). According to the four-compartment model derived from assessments of total body potassium and total body water, body cell mass and extracellular fluid volume increased significantly by 1.6 and 3.0 kg, whereas body fat decreased by 6.1 kg. Results obtained by the bioelectric impedance technique were similar. The mean (+/- SD) concentrations of insulin-like growth factor-I increased from 0.26 (0.06) at baseline to 2.56 (1.55) and 2.09 (1.03) kU/L after 6 and 26 weeks of treatment. Calcium and serum phosphate, osteocalcin, and procollagen-III concentrations were significantly higher, and intact PTH concentrations were reduced after 6 and 26 weeks of treatment, respectively. Total and free T3 concentrations were significantly increased after 6 and 26 weeks of treatment, whereas free T4 concentrations were reduced at 6 weeks, but after 26 weeks, free T4 concentrations had returned to pretreatment values. Finally, after 26 weeks of treatment, there was a decrease in the Comprehensive Psychological Rating Scale score (P < 0.05). The results show that GH replacement in GHD adults results in marked alterations in body composition, fat distribution, and bone and mineral metabolism and reduces psychiatric symptoms. Finally, we conclude that the observed beneficial effects of replacement therapy with GH are of sufficient magnitude to consider treatment of GHD adults.