Suppression of xenogeneic local graft versus host reaction by rat fetal spleen cells

Xenogeneic local graft versus host reaction was induced by the injection of 5 X 10(7) adult rat spleen cells under the capsule of cyclophosphamide-treated adult mice. A significant decrease in the reaction, measured by the kidney enlargement index, was obtained by adding to the reacting cells 5-20% of fetal rat spleen cells. Fetal rat thymocytes of fetal mouse splenocytes were not found to be inhibitory. The suppressive activity of rat spleen cells waned completely on day 3 of the postnatal life.     

供体骨髓输注减轻同种肝移植排斥反应

目的:研究非清髓性骨髓移植在同种肝移植免疫反应中的作用及其意义。 方法:动物实验为同种大鼠肝移植：Ⅰ组为Wistar→Wistar同基因对照组；Ⅱ组为SD→Wistar急性排斥组；Ⅲ组为SD→Wistar环孢素A（cyclosporine A,CsA）肌肉注射处理组；Ⅳ组为SD→Wistar术前1周大剂量供体骨髓细胞输注处理组。用术后一般状态、生存时间、病理学排斥分级、肝标本中IL-2、IFN-γ的表达以及胸腺内嵌合体的检测等手段，确定不同处理组移植后的排斥反应情况及机体的免疫状态。 结果:Ⅰ组大鼠术后无排斥反应发生；Ⅱ组大鼠术后9-13 d内全部死亡，中位存活时间（10.7±0.5）d，排斥反应明显；Ⅲ组大鼠仅见轻度排斥；Ⅳ组自然存活亚组6只大鼠4只长期存活 (>100 d)，排斥分级明显低于Ⅱ组（P<0.05）,与Ⅱ组相比，Ⅳ组IL-2、IFN-γ蛋白的表达均明显下调。在骨髓输注15 d后，用PCR法在雌性Wistar大鼠受体胸腺内可检测到雄性SD大鼠供体特异性的Y染色体（Y-chromosome-specific sequence，Sry）基因片段。 结论:供体骨髓输注可形成供受体细胞的嵌合状态，可降低同种异体肝移植的排斥反应，延长受体生存时间。     

供者源性的骨髓间质干细胞对急性移植物抗宿主病的影响

目的:采用大鼠骨髓移植模型探讨共移植供者源性的骨髓间质干细胞(MSCs)对骨髓移植后急性移植物抗宿主病(GVHD)的影响。方法:体外培养Fisher344大鼠骨髓间质干细胞,扩增至第5代用于移植。建立大鼠异基因急性GVHD模型(F344→Wistar)。受者Wistar大鼠采用致死性全身照射预处理,当天移植F344大鼠骨髓细胞和脾细胞。实验组则移植F344大鼠骨髓细胞、脾细胞和第5代的MSCs。观察各组移植后急性GVHD的发生时间、发病率和存活时间。结果:共移植MSCs推迟急性GVHD的发病时间,延长该组的存活时间,但无法完全消除急性GVHD的发生。结论:MSCs在体内具有免疫抑制功能,供者来源的MSCs在不使用免疫抑制剂情况下,可推迟急性GVHD的发病时间和延长受者的存活时间。     

Local graft versus host reaction in the xenogeneic system.

The injection of viable rat spleen cells beneath the renal capsule of cyclophosphamide (CY)-treated adult mice produced a localized graft versus host reaction (GvHR), manifested by the kidney enlargement index (KI). The optimal xenogeneic GvHR was obtained after injection of 30-50 million rat spleen cells into mouse recipients treated 24 hr before with CY, 200 mg/kg intraperitoneally (i.p.), and killed 7 days later. Splenomegaly in recipient mice suggested systemic dissemination of the local GvHR.     

Increased serum IgE concentrations during infection and graft versus host disease after bone marrow transplantation.

Serum IgE concentrations estimated in 25 bone marrow transplant recipients during episodes of infection or graft versus host disease, or both, were raised not only in some patients with acute graft versus host disease but also in many patients with infection. Raised values were not seen in chronic graft versus host disease. The routine estimation of serum IgE in bone marrow transplant recipients had minimal value because of the lack of specificity of the IgE response.     

Participation of phytohemagglutinin-transformed mouse lymphocytes in the graft versus host reaction

Transformed lymphocytes obtained by stimulating lymph node cells of CBA mice with phytohemagglutinin (PHA) do not give the graft versus host reaction (GVHR) if injected into sublethally irradiated (CBA×C57BL/6) F₁ hybrids. In a population of PHA-stimulated cells the GVHR was induced by small lymphocytes having the same concentration of antigens, detectable by antilymphocytic serum, as intact lymphocytes.Department of Immunology, Medico-Biological Faculty, N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR Yu. M. Lopukhin.) Translated from Byulletin' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 9, pp. 1096–1098, September, 1976.     

Immunoelectron microscopy of acute graft versus host disease of the skin after allogeneic bone marrow transplantation.

AIMS--To clarify the pathological mechanisms of acute cutaneous graft versus host disease (GvHD) following allogeneic bone marrow transplantation. METHODS--Skin biopsy specimens from five patients were examined by immunoelectron microscopy. A panel of monoclonal antibodies against T cell and natural killer cell subpopulations was used, including anti-CD4, -CD8, -CD16b, -CD56, -CD57, and -TCR delta 1 antibodies. RESULTS--All the specimens contained CD8+ cells, CD4+ cells, and CD56+ cells infiltrating the epidermis. Cells stained with anti-CD16b, -CD57, or -TCR delta 1 were very sparse or absent. Most of the CD8+ cells in the epidermis displayed morphological features of activated cytotoxic T lymphocytes and apposition of such cells to degenerating keratinocytes was shown. CD4+ cells outnumbered CD8+ cells in the epidermis in all five cases. Noticeable intercellular as well as intracellular oedema of keratinocytes was observed at the site of prominent CD4+ cell infiltration, suggesting that these also have a role as actual effector cells by secreting cytotoxic cytokines. CD56+ cells infiltrating the epidermis did not exhibit the characteristic ultrastructural morphology of the natural killer cells thus far examined, and their lineage remained uncertain. CONCLUSIONS--These data provide direct evidence that CD8+ cytotoxic T cells attack keratinocytes, and further suggest that CD4+ cells as well as CD56+ cells participate in the cellular pathogenesis of acute cutaneous GvHD.     

Immunocompetence of lymphocytes from pregnant mice studied in graft versus host reaction

The ability of lymphocytes taken during the second trimester from C57BL/6 mice mated with CBA males to induce the graft versus host reaction in (CBAxC57BL/6)F₁ hybrids was weaker than that of cells both of virgin donors and of mice pregnant after syngeneic mating. This was reflected in lengthening of the life span of the experimental recipients and weakening of inhibition of endogenous colony formation in the spleen of sublethally irradiated hybrids. This ability was restored at the end of pregnancy and in some experiments it actually exceeded the control.Department of Microbiology, Smolensk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Zhukov-Verezhnikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 3, pp. 310–312, March, 1977.     

Immunoglobulins and antibody formation in mice during the graft versus host reaction

During the GVH reaction produced in adult (C57B1 ☿×CBA ♂) F₁ hybrid mice by injection of C57B1 cells a profound drop in serum immunoglobulin levels was observed. The fall in IgG and IgA values was not reversed by antigenic stimulation with BSA, but the IgM level rose somewhat after BSA though never to the level seen in immunized controls. The antibody response to BSA, as measured by passive haemagglutination, was grossly depressed in experimental animals. Animals undergoing the GVH reaction showed less local inflammatory response at the site of Freund''s adjuvant injection than did controls. The possible importance of this immunoglobulin deficiency in the clinical presentation of the GVH syndrome is considered.     

Modified method of injecting parental lymphocytes to induce a local graft versus host reaction

A new method of injecting parental lymphocytes into the foot of F₁ hybrid mice to induce a local graft versus host reaction, based on the use of the Achilles' tendon as a natural shutter covering the lumen of the wound channel, is suggested. The new method of injection greatly simplifies the test and enables the conditions for its performance to be standardized. The low cell concentration in the working suspension enables it to be kept on ice without any significant increase in the percentage of dead cells.Department of Microbiology, Smolensk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Zhukov-Verezhnikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 8, pp. 238–239, August, 1979.     

Ability of lymphocytes stimulated by phytohemagglutinin in vitro to participate in the graft versus host reaction

Lymph node cells from CBA mice stimulated for 2 h by phytohemagglutinin were more able, whereas cells cultivated for 44 h with phytohemagglutinin were less able, than intact lymph node cells to participate in the graft versus host reaction when injected into sublethally irradiated (CBA x C57BL/6)F₁ hybrids. Syngeneic lymphocytes and killed allogeneic lymphocytes cultivated in the same way, like phytohemagglutinin itself, had no such action.Department of Immunology, N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR Yu. M. Lopukhin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 5, pp. 579–581, May, 1976.     

A study of the lymph-node type of graft versus host reaction in mice

A local form of the graph versus host reaction (GVHR) was induced in adult (CBA×C57BL)F₁ hybrid mice by subcutaneous injection of semiallogeneic spleen, thymus, or bone marrow cells from CBA mice into the right hind footpad. The criteria of activity of the GVHR were an increase in the number of blast forms in the region of popliteal lymph node and in its weight 7 days after transplantation of cells. After transplantation of 5×10⁶ and 20×10⁶ spleen cells the absolute weight of the regional lymph node was increased by 3–5 times and was significantly higher than in the control (injection of living syngeneic or fragmented semiallogeneic cells from the same source). By contrast with the control, in the experimental animals the effect clearly depended directly on the dose of transplanted cells. Enlargement of the lymph nodes was accompanied by the regular appearance of blast forms in them. Thymus and bone marrow cells had a much weaker action than spleen cells.Department of General Pathology, Institute of Clinical and Experimental Medicine, Academy of Medical Sciences of the USSR Siberian Division, Novosibirsk. (Presented by Academician of the Academy of Medical Sciences of the USSR V. P. Kaznacheev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 3, pp. 338–339, March, 1976.