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.     

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.     

Ability of cells of the regenerating spleen to effect the graft versus host reaction

The ability of cells of the regenerating (after single or twice repeated resection) and intact spleen of mice to induce the graft versus host reaction was studied by two methods. The regenerating spleen was shown to be less capable than the intact of bringing about this reaction.Laboratory of Growth and Development, Institute of Human Morphology, Academy of Medical Sciences of the USSR. I. M. Sechenov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 3, pp. 373–374, March, 1976.     

Development of the graft versus host reaction and its effect on pregnancy in mice after heparin administration

The effect of heparin on the graft versus host reaction (GVHR) was studied in mice and the character of development of pregnancy in females surviving after the GVHR was noted. Preliminary injection of heparin into the recipients prevented their death from the GVHR or lengthened their life span. After injection of heparin into the donors or its addition to the transplanted cells, the GVHR was intensified. In mice surviving after the GVHR as a result of heparin administration, in 60–100% of cases abortion or intrauterine death of the fetus was observed during pregnancy (3–6 months after transplantation of the cells). When these females were again mated pathological pregnancies were observed less frequently, but some of the prog eny developed runt disease. No such disturbances of pregnancy were observed in mice receiving heparin alone or surviving after transplantation of lymphocytes alone. Pregnancy enhanced the GVHR induced previously in females after injection of heparin.Department of Microbiology, Smolensk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. M. Zhdanov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 3, pp. 312–315, March, 1977.     

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.     

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.     

Effect of major histocompatibility complex haplotype matching by C4 and MICA genotyping on acute graft versus host disease in unrelated hematopoietic stem cell transplantation

We explored whether matching of human leukocyte antigen (HLA) haplotypes between the recipient and donor of hematopoietic stem cell transplantation (HSCT) predicted by C4 and MICA typing is associated with the incidence of acute graft versus host disease (aGVHD). DNA preparations collected from a total of 81 recipient and donor pairs were used for PCR-based C4 subtyping and/or MICA sequence-based typing. Incidences of aGVHD were compared according to C4 and MICA matching. The six most common MICA alleles were MICA*008:01, *010:01, *002:01, *004, *009:01/049, and *012:01. Among the 59 unrelated pairs, HLA alleles were matched in 34 (57.6%). C4 subtypes were identical between the recipient and donor in 28 (82.4%) HLA-matched unrelated pairs, while MICA genotypes were matched in all HLA-matched unrelated pairs. In the 22 HLA-matched related pairs, all recipients showed identical C4 subtypes with their respective donors. In multivariate analysis, C4 mismatch was a significant risk factor associated with the development of aGVHD in unrelated HSCT (hazard ratio = 3.24, P = 0.006). PCR-based C4 subtyping is a simple method for assessing the genetic identity of the HLA region between a recipient and unrelated donor. This test would be also useful for prediction of aGVHD in HSCT.     

Graft versus host reaction in tissue culture: I. Lysis of monolayers of embryo mouse cells from strains differing in the H-2 histocompatability locus by rat lymphocytes sensitized in vitro

Rat lymphocytes cultured on mouse embryo cell monolayers produced large pyroninophilic cells (LPC) which lysed the mouse cells. The LPC that developed on monolayers of any particular strain of mouse (originator monolayers) were tested, by transfer, for their ability to lyse monolayers of other mouse strains. The distribution of lysis among the various strains of mouse revealed a definite pattern of specificity. Analysis of the H-2 allelic complement of the mouse strains tested suggests that the lymphocytes were sensitized upon exposure to the mouse embryo monolayers against one or more of the antigens determined by the H-2 locus. The presence or absence of one or all of the antigens in other strains determined whether monolayers of these strains were lysed completely, partially, or not at all. It was concluded that the cultures obtained are an in vitro reflection of the graft versus host immune reaction. It was produced in the tissue culture as a primary response by normal lymphocytes.     

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.     

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.     

Morphological changes in the late periods of life in mice born after induction of the graft versus host reaction in their mothers

Various organs of mice born after induction of a graft versus host reaction in their mothers during pregnancy were investigated histologically in the second year of life. Atrophic changes predominated in the lymphoid tissue and amyloidosis was observed in the spleen and liver of many (61.2%) mice. Infiltration with lymphocytes was found in the liver, kidneys, lungs, and heart; some mice developed glomerulonephritis, vasculitis, and degeneration of the liver. Tumors of the lymphoid tissue were found in 17.7% of cases, compared with only 4.1% of cases in the control group of mice of the same age. Some of the tumors were transplanted into adult F₁ mice. The cell-free extract, if injected into newborn mice, did not induce the development of tumors during observation for 14 months.Departments of Microbiology and Pathological Anatomy, Smolensk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp. 111–114, July, 1979.     

Effect of cortisone-resistant thymocytes on endogenous colony formation in inbred mice

Endogenous colonies were counted in the spleen of sublethally irradiated (CBAxC57BL/6)F₁ hybrid mice after injection of thymocytes and lymph node cells treated with hydrocortisone and in intact CBA mice. Cortisone-resistance thymoctyes did not inhibit endogenous colony formation, whereas lymph node cells had a marked suppressive effect on endogenous colonies. In individual recipients the number of colonies in the spleen after injection of cortisone-resistant thymocytes was twice the number found in control irradiated hybrids.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. 84, No. 7, pp. 66–68, July, 1977.     

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.     

氨茶碱对移植物抗宿主反应及同种心脏移植物存活时间的影响

本文报告氨茶碱对移植物抗宿主反应及同种异位心脏移植物存活时间的影响。结果表明,人类T细胞在体外对氨茶碱共同温育后可分为茶碱抵抗(TR)和茶碱敏感(TS)两种,它们可分别增强和抑制总T细胞所引起的移植物抗宿主反应(GVHR)。给小鼠胃饲氨茶碱,其脾脏淋巴细胞所引起的GVHR也较胃饲生理盐水者为弱,提示氨茶碱在体内也可诱导具有免疫抑制作用的细胞。在此基础上,观察了氨茶碱对小鼠同种异位心脏移植物存活时间的影响,结果表明它可显著延长小鼠移植物的存活时间。     

Function of neutrophils in nonphlogogenetic reaction

Clinically nonphlogogenetic phagocyte reaction under conditions of bacterial challenge was studiedin vivo. The “mission” of phagocytes under such conditions is completed by evacuation of phagocytized bacteria from the site of capture into the blood and then into the intestine. The purulent process induced by massive doses ofStaphylococcus aureus (25×10⁶ and 25×10⁸ bacteria), without any concomitant injury to the peritoneum does not lead to the development of inflammation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 9, pp. 356–360, September, 1997     

Changes in H-alloantigen-recognition function of lymphocytes after hydrocortisone administration in mice

The ability of spleen, thymus, and bone-marrow cells of intact (control) and hydrocortisone-treated (experiment) CBA mice to induce a lymph node graft versus host reaction (GVHR) in (CBA×C57BL)F₁ hybrids was compared. After injection of hydrocortisone into the donors in a dose of 2.5 mg per mouse their spleen cells induced a more active GVHR, as shown by an increase in the lymph node indices and in the percentage of immunoblasts in the regional (popliteal) lymh node compared with the control. After transfer of thymus cells of hydrocortisone-treated donors the number of immunoblasts was higher than, but the weight of the lymph node was almost the same as in the control. Conversely, after injection of bone marrow cells from hydrocortisone-treated donors, the lymph node enlarged whereas the percentage of immunoblasts did not increase above the control. Consequently, when the increase in the hydrocortisone level is exogenous in nature, the cell populations of the spleen and thymus contain a higher proportion of T lymphocytes, which respond by proliferation to contact with H alloantigens.Institute of Clinical and Experimental Medicine, Academy of Medical Sciences of the USSR, Siberian Branch, 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. 84, No. 10, pp. 458–459, October, 1977.     

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.     

The role of the lymphatic system in the changes of electrolyte balance in the febrile reaction

The shifts of the electrolyte level in the lymph and blood are of the same direction, namely, increased. The content of potassium, sodium, and calcium changes only after prolonged fever, while that of magnesium changes after just a single administration of pyrogenal. The lymph level of calcium and magnesium rises more significantly as compared to the blood. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 2, pp. 174–176, February, 1994     

Tumorigenicity of mouse T lymphoma cells is controlled by the level of major histocompatibility complex class I H-2Kk antigens

We have previously found that an increased tumorigenicity and spontaneous metastatic potential of BW5147-derived T lymphoma cells was associated with a decrease in major histocompatibility complex (MHC) class I H-2K^k antigen expression. This suggested that H-2K^k antigens may control the tumorigenic potential of BW T lymphoma cells. Our current experiments aimed to prove this association by specifically altering H-2K^k expression by gene transfection. Transfected cells expressing a high level of H-2K^k antigens were significantly less tumorigenic and metastatic after subcutaneous inoculation. However, there was selectionin vivo for cells expressing a reduced level of H-2K^k antigens, which concomitantly led to an increased tumorigenicity. These data further confirmed the strong association between H-2K^k expression and tumorigenicity. We subsequently tested whether the immune system is implicated in this phenomenon by inoculating the H-2K^k transfectants into irradiated, immunocompromised recipients. Our results indicate that the reduced tumorigenicity of the BW H-2K^k transfectants is due to an immune rejection mechanism, mediated by CD8⁺ immune effector cells, as revealed byin vivo depletion experiments with anti-CD8 antibodies. Hence, we hereby demonstrated that H-2K^k antigens increased the immunogenicity of BW cells, via a CD8-dependent mechanism, which consequently reduced their tumorigenicity.