Functional state of the thyroid gland during systemic graft vs host reaction

Triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) serum content was measured in mice during systemic "graft-versus-host" reaction (GVHR), using radioimmunoassay. It was demonstrated that on the 3rd day after GVHR induction the levels of these hormones did not differ from the control values. T3 and T4 concentrations and 125I absorption by thyroid gland diminished by day 10. At the same time TSH level remained unchanged. On day 24 after GVHR induction T3 and T4 content was significantly reduced, although TSH concentration exceeded the control value. 125I absorption was enhanced as compared to the value observed on day 10. The data obtained show the vigorous inhibition of thyroid gland function during systemic GVHR.     

Immunosuppressive role of the liver in the graft versus host reaction]

The ability of the liver to reduce the intensity of the graft versus host (GVH) reaction has been investigated in F1 hybrid rats implanted with parental lymph nodes. Intrahepatic and intrarenal tissue implantations were compared using classical GVH criteria. The intrahepatic implantation of lymph nodes suppress the mortality observed after intrarenal implantation. The results confirm the interest of portal drainage in organ transplantation and suggest a new site of implantation for lymphoid cells.     

Origin and nature of the cells participating in the popliteal graft versus host reaction in mouse and rat.

The origin and nature of the cells accumulating in the popliteal lymph node graft versus host reaction (GVHR) of mice and rats were studied by karyotypic analysis, immunofluorescence, and radioautography after [³H]thymidine incorporation. At all times explored, the proliferating cells represented at most 10% of the cells, and among them the frequency of mitoses of donor origin was about 50, 15, and 4% on the third, seventh, and fifteenth days, respectively. Using alloantisera, no significant numbers of donor T cells could be detected among the resting lymphocytes. On the seventh day, the enlarged nodes contained at most 2% of donor cells and about two-thirds of T and one-third of B lymphocytes, i.e., a cell composition comparable to that of normal lymph nodes, except for an increased proportion of lymphoblasts and plasmablasts. Some plasmablasts secreted antibodies against sheep red blood cells, probably reflecting polyclonal activation of B cells. Popliteal GVHRs in T-depleted F₁ mice were of comparable intensity, with no increase in the proportion of donor cells, and the enlarged nodes contained a high proportion of B lymphocytes and plasmablasts of host origin.     

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

Cells of the spleen or lymph nodes of CBA mice were transplanted to sublethally irradiated (CBAXC57BL/6)F1 mice; this caused development of the graft-versus-host reaction (GVHR). Lymphocytes lost the capacity to realize this reaction after in vitro treatment with specific sera against mouse T- and B-lymphocytes. Apparently, development of the GVHR in mice was connected with the cooperative interaction of T- and B-lymphocytes.     

Duodenal immunoglobulin deficiency in graft versus host disease (GVHD) mice.

The small intestine is a well documented target organ in mouse and human GVHD, and diarrhea is a prominent part of the clinical GVHD syndrome. Although a plethora of systemic immune deficits has been documented in GVHD, the integrity of the small intestinal immune system has not been investigated. A correlation has not been demonstrated between systemic immune dysfuction and the incidence of lymphomas in mouse GVHD survivors. If gastrointestinal immune deficiency exists in mouse GVHD, its possible relationship to GVHD lymphomas, frequently abdominal. should be investigated. GVHD was produced in newborn BLA (C57 BL/Ka females x BALB-C males) mice house in a specific pathogen-free environment by the i.p. inoculation of 10(7) male BALB-C spleen cells. Control mice received syngeneic spleen cells. Twenty GVHD and 16 control mice were sacrificed at 3 weeks and specimens of duodenum were removed for routine histologic and immunofluorescent examination. All but one GVHD mouse (95%) had virtually absent duodenal IgA and IgM. Duodenal cellular fluorescence was demonstrated in all controls. A significant duodenal immunoglobulin deficit has been demonstrated in 3-week-old GVHD mice. The relationship of this finding to GVHD diarrhea, wasting, and neoplasia remains to be determined.     

The pretransplant systemic metabolic profile reflects a risk of acute graft versus host disease after allogeneic stem cell transplantation

Metabolomics - Allogeneic stem cell transplantation is used in the treatment of younger patients with severe hematological diseases, especially hematological malignancies, and acute graft versus...     

Concomitant changes in adenylate cyclase and cytolytic activities of lymphoid cells during graft versus host reaction.

Spleen cells from adult F1 hybrid mice undergoing the graft versus host reaction due to the inoculation of lymphoid cells of parental origin showed increased adenylate cyclase activity and cytolytic activity. A time-course study revealed that both the adenylate cyclase and cytolytic activities started increasing at Day 4 and reached maximum at Day 8 of initiation of the graft versus host reaction. Furthermore, the magnitude of both adenylate cyclase activation and cytolytic activity were dependent upon the number of parental cells injected into the F1 hybrid recipients. Elevated adenylate cyclase activity was also observed in spleen cells from irradiated animals undergoing the graft versus host reaction in which the nonspecific, but not the specific cytolytic activity was markedly depressed.     

Recruitment of null cells during graft versus host reactions in the chicken

Untreated SC (B2/B2) chicken spleen or thymus cells (2 × 10⁷) caused significantly increased [³H]thymidine incorporation in spleens of heavily irradiated FP (B15/B21) recipient chicks on Day 4 after iv injection. Mitomycin-treated SC spleen cells or spleen cells treated with rabbit anti-T-cell serum and complement failed to raise the [³H]thymidine incorporation over that in uninjected, bursa cell-injected or FP spleen cell-injected controls. However, the combination of mitomycin-treated spleen or thymus cells and anti-T-treated spleen cells caused an increased [³H]thymidine uptake, suggesting the recruitment of non-T cells into proliferation by alloreactive mitomycin-treated T cells. Bursa cells did not proliferate during GVH reactions even though they could be shown to undergo proliferation in vivo upon mitogen (lipopolysaccharide and dextran sulfate) stimulation. In contrast, anti-T-treated spleen cells from agammaglobulinemic chickens were recruited into proliferation, suggesting that the recruited cell was not only not a T cell, but also no pre-B or B cell and most likely represented a cell of the monocyte-macrophage series.     

Effect of graft versus host reaction on cell cycle time in neonatal mouse jejunum

Abstract. The duration of cell cycle parameters in control mouse jejunum has been compared with that found following induction of a graft-versus-host reaction (GvHR) during the first 3 weeks of postnatal life.
Values for t_c , and t_G1 were found to decrease progressively during normal development: estimates for the whole crypt column in 21-day-old mice were approximately half to one quarter those found 6 days after birth 12.1 ± 0.5 hr and 24.2 ± 0.3 hr for t_c ; 2.8 ± 0.3 hr and 12.1 ± 0.3 hr for t_G1 respectively; (means ± SE). t_S and t_G2 were found to remain approximately constant during this period of neonatal development.
Injecting foreign spleen cells into 3-day-old mice produced no effect on crypt cell proliferation or cell cycle parameters measured 3 days later. GvHR mice studied 8 days after spleen cell injection, however, showed both an increase in crypt cell proliferation and decreases in the values for t_c and t_G1 , to levels similar to those normally found in 21-day-old control animals ( t_c 12.4 ± 0.4 hr and t_G1 5.4 ± 0.4 hr for 11-day-old GvHR mice). The possible mechanism leading to these changes is discussed.
The ability of GvHR to stimulate cell proliferation is used in the present work to test the hypothesis that the total number of cell divisions taking place after birth determines the temporal sequence of changes in disaccharidase content produced during neonatal development.     

Effect of graft versus host reaction on cell cycle time in neonatal mouse jejunum

The duration of cell cycle parameters in control mouse jejunum has been compared with that found following induction of a graft-versus-host reaction (GvHR) during the first 3 weeks of postnatal life. Values for tc and tG1 were found to decrease progressively during normal development: estimates for the whole crypt column in 21-day-old mice were approximately half to one quarter those found 6 days after birth 12.1 +/- 0.5 hr and 24.2 +/- 0.3 hr for tc; 2.8 +/- 0.3 hr and 12.1 +/- 0.3 hr for tG1 respectively; (means +/- SE). tS and tG2 were found to remain approximately constant during this period of neonatal development. Injecting foreign spleen cells into 3-day-old mice produced no effect on crypt cell proliferation or cell cycle parameters measured 3 days later. GvHR mice studied 8 days after spleen cell injection, however, showed both an increase in crypt cell proliferation and decreases in the values for tc and tG1 to levels similar to those normally found in 21-day-old control animals (tc 12.4 +/- 0.4 hr and tG1 5.4 +/- 0.4 hr for 11-day-old GvHR mice). The possible mechanism leading to these changes is discussed. The ability of GvHR to stimulate cell proliferation is used in the present work to test the hypothesis that the total number of cell divisions taking place after birth determines the temporal sequence of changes in disaccharidase content produced during neonatal development.     

Effect of prodigiosin and its combination with immunodepressants on the graft versus host reaction in mice

The local (lymph node) graft-versus-host reaction (GVHR) in F1 (CBA X C57BL/6) mice and the lethal GVHR in C57BL/6 mice were induced by transfer of lymph node cells of CBA mice with skin allotransplants from C57BL/6 mice. Prednisolone in combination with asathioprin (imuran) administered to CBA mice inhibited the GVHR. Prodigiosan used alone was not active, while in combination with immunodepressants it increased their inhibitory effect. Adhesive cells with a suppressive activity were detected in the spleen of mice treated with prodigiosan. Such cells were capable of suppressing the capacity of syngeneic lymphocytes for inducing the GVHR.