Secretion of a suppressor factor by mouse lymphocytes on contact with syngeneic erythrocytes

During incubation of spleen cells from (CBA x C57BL)F₁ mice immunized with rat erythrocytesin vitro with syngenetic erythrocytes a suppressor factor inhibiting the immune response to sheep's erythrocytes is secreted. On intravenous immunization the factor is secreted by thymus and spleen cells, but not by bone marrow or lymph node cells. The factor is probably antigen-nonspecific and is secreted by nonspecific T suppressors on contact with syngeneic erythrocytes.Department of Immunology, Central Research Laboratory, N. I. Pirogov Second Moscow medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR R. V. Petrov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 11, pp. 576–578, November, 1979.     

In utero treatment with monoclonal antibody to IL-2 receptor beta-chain completely abrogates development of Thy-1+ dendritic epidermal cells.

Interleukin-2 (IL-2), a crucial growth factor for mature T lymphocytes, is produced in fetal thymus under developmental control, although its biological significance remains unclear. We found that the two distinct subunits of the IL-2 receptor, i.e. the alpha-chain (IL-2R alpha) and the beta-chain (IL-2R beta), were expressed in an almost mutually exclusive fashion throughout fetal thymus ontogeny, and that the blockade of IL-2R beta, a signal transducing component of IL-2R, by administering a neutralizing mAb to IL-2R beta resulted in the complete and selective disappearance of Thy-1+ skin dendritic epidermal cells. Development of any other T cell subsets was uncompromised. This indicates that IL-2 plays a crucial role in the development of fetal V gamma 5+ cells and their descendants.     

Membrane-associated nucleotide pyrophosphatase activity on leucocytes from different compartments

The distribution of membrane-associated nucleotide pyrophosphatase activity has been investigated on mouse leucocytes of different origin. It is shown that enzyme-specific activity is higher on bone-marrow cells than on cells derived from peripheral organs. Since thymus lymphocytes show the lowest activity, it is obvious that the thymus environment can influence the enzyme activity on bone-marrow stem cells which have entered this organ. Spleen cells from thymus-deficient nude mice displayed more enzyme activity than spleen cells from normal mice, although the percentage of lymphocytes was similar in both donor-cell populations.     

Expression of CD21 is developmentally regulated during thymic maturation of human T lymphocytes.

CD21, the C3d/CD23/Epstein-Barr virus (EBV), receptor is expressed at low density on cells of the T lineage. Immature thymocytes express CD21 with high density. In the present study, we have analyzed the expression of CD21 during intrathymic maturation of T cells. An intense staining for CD21 was observed at the double-negative stage and at the stage of early acquisition of CD4. CD21 expression was decreased at the double-positive and single-positive stages, to then reach levels similar to those of peripheral blood T cells. Staining of thymus sections showed a bright fluorescent signal on thymocytes entering the thymus in the cortical region. Taking advantage of the immature phenotype of cells expressing high amounts of CD21 (CD21(++)), we depleted thymocyte suspensions in CD3(+) and CD8(+) cells to study the properties of CD21 on this cell subset. Triggering of CD21 with its ligands iC3b, CD23 and anti-CD21 mAb did not alter the proliferative response of thymocytes to IL-7, and did not induce the differentiation of early cells into CD4(+)CD8(+) thymocytes. Immunoprecipitation did not reveal any molecule associated with CD21 that could play a signaling role in thymocytes. Finally, EBV induced a down-regulation of CD21 and an up-regulation of CD1 in CD21(++) thymocytes. Taken together, our observations demonstrate a regulated expression of CD21 on human thymocytes and suggest that the CD21(++) subset may be a target for EBV. We further suggest that CD21 on early thymocytes acts as a ligand for CD23-expressing cells in the thymus.     

T cell receptor β chain dimers on immature thymocytes from normal mice

During T cell development the T cell receptor (TCR) β chain is expressed before the TCRα chain. Experiments in TCRβ transgenic severe combined immune deficiency (SCID) mice have shown that the TCRβ protein can be expressed on the cell surface of immature thymocytes in the absence of the TCRα chain and that the TCRβ protein controls T cell development with regard to cell number, CD4/CD8 expression and allelic exclusion of the TCRβ chain. Subsequent experiments have shown that on the surface of thymocytes fromTCRβ transgenic SCID mice the TCRβ protein can be expressed in a monomelic and dimeric form whereas only the dimeric form was found on the surface of a TCRβ-transfected, immature T cell line. The results presented here show that normal thymocytes from 16-day-old fetuses likewise express only the dimeric form and that the monomelic form on the surface of thymocytes from transgenic mice results from glycosyl phosphatidylinositol linkage. Our results show for the first time that under physiological conditions a TCRβ dimer can be expressed on the cell surface without the TCRα chain.     

低剂量电离辐射对小鼠肺、胸腺和脾细胞分泌CSF的影响

本实验采用X射线对小鼠全身照射, 剂量率为12.5mGy/mIn, 剂量为25～250mGy。发现低剂过辐射能明显刺激肺和胸腺细胞分泌造血细胞集落刺激因子(Colony-stimulating factors,CSF)。胸腺细胞反应较为敏感，50mGy即能明显促进CSF分泌，250mGy时胸腺细胞分泌CSF活性水平仍明显高于对照(P<0.01)，且以50mGy剂量照射对其分泌CSF的刺激作用最强;肺组织细胞反应较弱，仅在75mGy剂量照射后.CSF分泌量明显增加(P<0.05):低剂量照射对脾细胞分泌CSF未见有明显的促进作用。75mGy照射后不同时间检测CSF,发现照射后2天肺和胸细胞分泌CSF量明显增加，直到照射后7天，CSF活性水平仍明显高于对照(P<0.01)，说明低剂量X射线全身照射能明显 促进肺和胸腺细胞分泌CSF，这对促进机体造血和免疫功能，增强机体抵抗力有重要的意义.     

Deficiency of UV-induced excision repair in human thymocytes

The capacity of human thymocytes and of differentiated lymphocytes circulating in peripheral blood to perform unscheduled DNA synthesis (a measure of nucleotide excision repair) after UV irradiation was measured by radioautographic analysis. Only 4% of immature T lymphocytes, but 68% of circulating lymphocytes exhibited unscheduled DNA synthesis. When UV sensitivity of peripheral blood lymphocytes and thymocytes from the same donor were compared, the thymocytes, in each case, were significantly more UV sensitive than were the circulating lymphocytes. Peripheral blood lymphocytes from subjects undergoing halothane and morphine anesthesia during surgery showed 56% less excision repair capacity than those from unanesthetized donors. The difference occurred in the number of cells capable of repair rather than in the extent of repair synthesis per cell. Ultraviolet-induced unscheduled DNA synthesis occurred in only 3% of the thymocytes removed from rats killed by cervical dislocation. Therefore, the deficiency of excision repair was observed in rat thymocytes which had not been affected by anesthesia or surgical trauma. Since the thymus contains more than 90% immature T-cells, our results indicate that immature T-cells are deficient in nucleotide excision repair whereas the majority of mature peripheral blood lymphocytes exhibit such repair.     

Coevolution of TCR-MHC interactions: conserved MHC tertiary structure is not sufficient for interactions with the TCR

The specificity for self-MHC that is necessary for T cell function is a consequence of intrathymic selection during which T cell antigen receptors (TCRs) expressed by immature thymocytes are tested for their affinity for self-peptide:self-MHC. The germ-line-encoded segments of the TCR, however, are believed to have an innate specificity for structural features of MHC molecules. We directly tested this hypothesis by generating a transgenic mouse system in which the protein HLA-DM is expressed at the surface of thymic cortical epithelial cells in the absence of classical MHC molecules. The specialized intracellular function of HLA-DM has removed this MHC class II-like protein from the evolutionary forces that have been hypothesized to shape TCR-MHC interactions. Our study shows that a structural mimic of MHC class II is not sufficient to appropriately interact with the TCRs expressed by developing thymocytes. This result emphasizes the unique complementarity of TCR-MHC interactions that are maintained by the evolutionary pressures dictated by positive selection.     

Cellular and molecular correlates of the decline in responsiveness of cartilage and thymus to growth hormone in aged animals

The responses in vitro of cartilage to somatomedin and of thymocytes to growth hormone have been studied in tissues derived from rats of various ages. The basal and somatomedin stimulated incorporation of radioactive proline into proteins and of sulphate into mucopolysaccharides diminishes markedly with age. Chondrocytes per unit area in cartilage of old rats are about 4- to 5-fold reduced in number as compared to those in cartilage from 1-day old rats. The organ size and yield of thymocytes are reduced in aged rats. Besides the fall in number of cells, the average metabolic activity of cells as measured by uridine incorporation into RNA in vitro is also diminished. There is a progressive decline in stimulation by growth hormone of uridine incorporation in isolated thymocytes with age. Immunocytochemical studies reveal the location of the hormone along the membrane. The amount of the hormone bound by thymocytes, estimated by immunoenzymatic methods is 3- to 9-fold lower in thymocytes from 14-months old rats as compared to similar preparations from 4-week old rats. Thymocytes from both young and old rats are composed of subpopulations, one of which binds growth hormone. The proportion of the hormone binding cells is higher in thymocytes from young rats as compared to those from aged animals.