Selective sparing of enterochromaffin cells in graft versus host disease affecting the colonic mucosa

Graft versus host disease affecting the large bowel causes destruction of the crypt epithelium. There is a selective sparing of enterochromaffin cells in the majority of cases. As a consequence, single as well as small clumps of enterochromaffin cells are to be seen in the sites formerly occupied by the destroyed crypt epithelium. The reason for this phenomenon is unclear, but it may be related to the fact that the enterochromaffin cells are end-stage and non-proliferating cells. This is useful diagnostically. However, cytotoxic drugs or irradiation must be excluded as the cause of the mucosal damage to bowel as there are theoretical reasons to expect that a similar phenomenon will be seen after these forms of therapy.     

The histological diagnosis of cutaneous graft versus host disease: relationship of skin changes to marrow purging and other clinical variables

Punch biopsies of skin were taken from allogeneic marrow recipients routinely before transplantation, at 14-22 and 90-107 d after grafting and in the event of a clinical rash. Three histological appearances were encountered: graft versus host disease (GvHD), epidermal abnormalities, and normal. Graft versus host disease was characterized by epidermal basal vacuolation, spongiosis and individual cell necrosis associated with mononuclear cell infiltration of the upper dermis and lower epidermis, while epidermal abnormalities were identical to GvHD but without the mononuclear cell infiltrate. Graft versus host disease occurred only in patients receiving marrow unpurged of T-cells while epidermal abnormalities occurred with equal frequency in recipients of purged and unpurged marrow and were also noted in a high proportion of pre-transplant biopsies. Patients whose skin biopsies exhibited epidermal abnormalities showed no greater incidence of subsequent clinical or histological GvHD than those with normal biopsies. For these reasons, we conclude that epidermal abnormalities cannot be regarded as a minor manifestation of GvHD as has often been previously assumed. We also conclude that they cannot be regarded as the cause of a rash as, unlike GvHD, the incidence was not significantly different in patients with and without rashes. The cause of epidermal abnormalities is not entirely clear; cytotoxic drugs and irradiation appear to play a part but their occurrence in patients with previously normal post-transplant biopsies suggests that other factors may also be important. Some patients with strong clinical evidence of GvHD had negative biopsies; these should be regarded with caution especially within the first 24 h after the onset of a rash as the diagnostic histological picture may take time to develop. In some cases, GvHD was confined to pilosebaceous units; this seems to represent a minor form of the disease with only a limited capacity for progression. Dysplastic epidermal changes which have previously been attributed to the use of cyclosporin A were found with equal frequency in patients who did not receive this drug and must therefore have some other cause.     

树突状细胞亚群与急慢性移植物抗宿主病的关系

目的探讨树突状细胞（DCs）亚群在急慢性移植物抗宿主病（GVHD）中的作用。方法通过三色流式细胞仪检测异基因造血干细胞移植患者7例发生aGVHD前后和8例cGVHD治疗前后外周血DC1、DC2变化。结果发生aGVHD时患者DC1、DC2百分数及绝对数均明显低于发生aGVHD前水平,二者相比DC1、DC2百分数及绝对数均具有统计学意义（P〈0．05）。GVHD（＋）组DC1、DC2水平均低于GVHD（-）组,其中DC2百分数和绝对数两组相比具有统计学意义（P〈0．05）。aGVHD治疗后DC1、DC2百分数和绝对数均较发生aGVHD时有所增加,aGVHD治疗后与发生aGVHD时DC1、DC2百分数和绝对数对比较,均具有统计学意义（P〈0．05）。发生cGVHD患者DC1、DC2百分数与正常健康人外周血DC1、DC2百分数相比具有统计学意义（P〈0．05）。治疗后cGVHD患者DC1、DC2百分数明显下降,与治疗前相比具有显著统计学意义（P〈0．05）。结论aGVHD患者外周血DC1、DC2是减少的,而cGVHD患者外周血DC1、DC2是增加的,尤其以DC2为显著。     

IL—10在急性移植物抗宿主病、移植物排斥中的作用

目的：研究异基因造血干细胞移植（allo-HSCT)中,细胞因子IL－10在急性移植物抗宿主病（aGVHD）、移植物排斥中的作用。方法：20例恶性血液病患者行allo-HSCT,采用双夹心酶联免疫吸附法（ELISA）检测移植前后血清IL－10的浓度,用逆转录聚合酶链反应法（RT－PCR）检测移植后外周血单个核细胞中IL－10mRNA的表达。结果：20例移植患者中6例发生Ⅰ度GVHD,4例Ⅲ-Ⅳ度GVHD,3例移植物排斥,移植前Ⅲ-ⅣGVHD和移植物排斥患者的血清IL－10浓度明显低于未发生的aGVHD患者,移植后发生aGVHD和移植物排斥患者IL－10水平下降,而未发生的aGVHD的患者IL－10水平明显提高,RT－PCR检测IL－10基因表达结果提示,发生aGVHD的患者移植后IL－10mRNA表达阳性率明显低于未发生GVHD患者。结论：IL－10对aGVHD和移植物排斥的发生起重要的负向调节作用。     

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.     

Immunologic disturbances in mice born after induction of a graft versus host reaction in the mother

The immunologic status of mice born after induction of a graft versus host reaction in the mother was studied. Lymphocytopenia, delayed rejection of skin allografts, a decrease in natural resistance to experimental typhoid infection, and a decrease in the number of plaqueforming cells in the spleen after immunization of the mice with sheep's red blood cells and typhoid Vi antigen were found at the age of 1 month. At the age of 2–3 months, the same changes together with a decrease in the number of T-lymphocytes in the spleen and lymph nodes were found only in mice with clinical features of runt disease. In the second year of life depression of the immune response to sheep's red blood cells and enhancement of the response to Vi antigen and a decrease in the number of T-lymphocytes in the spleen and lymph nodes compared with the control were observed in the progeny. An increased concentration of immunoglobulins and transferrins was found in the blood serum and antierythrocytic autoantibodies were detected in some mice.Department of Microbiology and Department of Biochemistry, Smolensk Medecal 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. 89, No. 2, pp. 200–202, February, 1980.     

Immunological basis for treatment of graft versus host disease after liver transplant

Graft versus host disease (GVHD) after liver transplant, although a rare disease, has a very high mortality rate. GVHD occurs due to immunoreactions caused by donor T lymphocytes and host cell surface antigens resulting in proliferation and clonal expansion of T lymphocyte. Migration of effector cells, including macrophages, NK cells and cytotoxic T lymphocyte, to the target organs such as skin, intestine and bone marrow results in skin rashes, diarrhea and bone marrow depression. GVHD is diagnosed by clinical symptoms, histopathological findings and by the presence of chimerism. The delayed diagnosis, opportunistic infections and lack of definitive treatment of post orthotopic liver transplant (OLT)-GVHD results in sepsis and multi-organ failure leading to very low survival rates. In this review, we have focused on early diagnosis and critically discuss novel treatment modalities to decrease the incidence of GVHD.     

Effect of burn trauma on reactivity of mouse spleen cells of different genotypes in the regional graft versus host reaction

Department of General Surgery, Smolensk Medical Institute. (Presented by Academician of the Academy of Medient Sciences of the USSR V. D. Fedorov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 6, pp. 592–594, June, 1990.     

Participation of mouse T and B lymphocytes in the graft versus host reaction

Transplantation of spleen or lymph node cells from CBA mice into sublethally irradiated (CBAxC57BL/6)F₁ mice induced the development of a graft versus host reaction (GVHR). The lymphocytes lost their ability to give this reaction after treatmentin vitro with specific sera against both mouse T lymphocytes and B lymphocytes. The development of the GVHR in mice is evidently connected with cooperative interaction between T and B lymphocytes.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. 6, pp. 713–715, June, 1976.     

Interaction between the graft versus host reaction and pregnancy

A graft versus host reaction (GVHR) was induced in F₁(CBA×C57BL/6) female hybrids by intravenous injection of a suspension of lymphocytes from the spleen and lymph glands from C57BL/6 females. Pregnancy, which developed as a result of crossing the experimental females with syngeneic males 1–10, 10–20, 30–40, and over 40 days after injection of the lymphocytes, aggravated the transplantation sickness due to the GVHR. On the other hand, the GVHR under these conditions reduced the percentage of animals that became pregnant and disturbed the reproductive function of the experimental mice (stillbirth, death of the pregnant females, abortion). An exacerbation of the GVHR was observed in some of the experimental animals after giving birth. The rate of survival of the progeny was lowered.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. 80, No. 9, pp. 68–71, September, 1975.     

Altered T‐cell entry and egress in the absence of Coronin 1A attenuates murine acute graft versus host disease

Acute graft‐versus‐host disease (aGvHD) is a major limitation to the use of allogeneic stem cell transplantation for the treatment of patients with relapsed malignant disease. Previous work using animals lacking secondary lymphoid tissue (SLT) suggested that activation of donor T cells in SLT is critically important for the pathogenesis of aGvHD. However, these studies did not determine if impaired migration into, and more importantly, out of SLT, would ameliorate aGvHD. Here, we show that T cells from mice lacking Coronin 1A (Coro 1A^?/?), an actin‐associated protein shown to be important for thymocyte egress, do not mediate acute GvHD. The attenuation of aGvHD was associated with decreased expression of the critical trafficking proteins C‐C chemokines receptor type 7 (CCR7) and sphingosine 1 phosphate receptor on donor T cells. This was mediated in part by impaired activation of the canonical NF‐κB pathway in the absence of Coro 1A. As a result of these alterations, donor T cells from Coro 1A^?/? mice were not able to initially traffic to SLT or exit SLT after BM transplantation. However, this alteration did not abrogate the graft‐versus‐leukemia response. Our data suggest that blocking T‐cell migration into and out of SLT is a valid approach to prevent aGvHD.     

罗丹明123介导的光动力学疗法预防急性移植物抗宿主病的实验研究

目的：探讨Rh123介导的光动力学疗法(PDT)预防异基因造血干细胞移植急性移植物抗宿主病(aGVHD)的可行性及安全性。 方法： 以C57B/6小鼠为供鼠，BALB/c小鼠为受鼠，建立小鼠异基因骨髓移植的aGVHD模型；混合脾脏淋巴细胞培养(MLC)加Rh123孵育，接受氩离子激光30 mW/cm2照射3 min，再与供者骨髓混合移植给受鼠，观察受鼠移植后造血重建、aGVHD发生情况及病理改变、生存率；流式细胞仪检测MLC细胞CD3+CD69+阳性率。 结果： 光动力学治疗组的aGVHD发生减少，肝、皮肤、肠道病理程度减轻，生存率显著高于未经光动力学治疗组；光动力学处理后的混合淋巴细胞培养24 h后，CD34+CD69+表达明显下降。 结论： Rh123介导的光动力学疗法可有效预防小鼠异基因骨髓移植的aGVHD。     

Suppression of interferon synthesis during the graft versus host reaction in (CBA×C57BL/6) F1 mice

During the development of the graft versus host reaction (GVHR) in (CBA×C57BL/6) F₁ mice after transplantation of spleen cells from mice of the parental C57BL/6 strain, production of serum interferon induced by intraperitoneal injection of Newcastle disease virus was sharply reduced. Interferon production was reduced and later completely abolished in cultures of bone marrow cells from mice during development of the GVHR. This phenomenon can serve as a criterion of the development of the GVHR.Department of Virology, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. Department of Microbiology, Smolensk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. D. Solov'ev.) Translated from Byulletin' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 9, pp. 1098–1100, September, 1976.     

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.     

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.     

Role of genetic differences between mother and fetuses in the development of a graft versus host reaction induced in the mother

Development of the graft versus host reaction (GVHR) was studied in female (CBA×C57BL/6)F₁ mice during pregnancy, and after birth or the day before mating with syngeneic, semisyngeneic, and allogeneic males. The development and outcome of the GVHR in the female mice was shown to depend on genetic differences between the donors of transplanted lymphocytes and the fetuses and also on the time of induction of the GVHR. If lymphocytes from C57BL/6 mice were injected into (CBA×C57BL/6)F₁ females after parturition or on the day before mating with males of the parental CBA line, pregnancy led to enhancement of the GVHR; if lymphocytes were injected during pregnancy, an increase in resistance to the BVHR was observed. In the case of mating with males of the contralateral parental line C57BL/6 (syngeneic with respect to the lymphocyte donors) pregnancy did not affect the development of the GVHR regardless of the time when the cells were injected.Department of Microbiology and Department of Biology, 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. 89, No. 3, pp. 340–342, March, 1980.