scholarly journals RAPID VIRAL INDUCTION OF MURINE LYMPHOMAS IN THE GRAFT-VERSUS-HOST REACTION

1972 ◽  
Vol 136 (6) ◽  
pp. 1533-1544 ◽  
Author(s):  
Eugene A. Cornelius

When weanling (SJL/J x C57BL/1)F1 hybrid mice were given five weekly-injections of small doses of viable SJL/J spleen cells, so as to induce a graft-versus-host reaction (GVHR), reticulum cell sarcomas were induced in all of the host mice by the 40th day after the first cell injection. Such tumors, on transplantation, were accepted by syngeneic (SJL/J x C57BL/1)F1 and C57BL/1 hosts, but not by SJL/J or NZB mice. Cell-free extracts of SJL/J spleens injected into similar hybrids resulted in identical tumors in all hosts within the same period; the transplantation characteristics were also similar. Normal (SJL/J x C57BL/1)F1 hybrids as well as similar hybrids injected with SJL/J liver or syngeneic F1 spleen cells did not develop tumors. Cell-free preparations of eight tumors induced in F1's by viable SLJ/J spleen cells were injected into newborn (C57BL/1 x A)F1 and C57BL/1 mice: tumors were induced, with seven of eight tumor preparations, with a latent period of 33–49 days. Such tumors were lymphosarcomas, and, in the case of (C57BL/1 x A)F1 hosts, further transplantation revealed that they were antigenically C57BL/1 tumors. These experiments provide conclusive evidence for a viral etiology of GVHR-induced tumors. Furthermore, tumor induction in the GVHR does not appear to depend specifically on an immunological mechanism but is most probably due to release or activation of a sufficient quantity of oncogenic virus within a certain time period in a highly susceptible host. Comparison with radiation induction of viral leukemia in mice revealed similarities in regard to optimal host age and the spacing of administration of the tumor-inducing agent. SJL/J mice carry a type C virus which causes a high incidence of spontaneous Hodgkin-like tumors by 1 yr of age; C57BL/1 mice do not develop lymphomas spontaneously but carry a latent leukemogenic virus. Their hybrid also has a low incidence of spontaneous lymphomas. Based on the results of these and previous experiments, the viruses of these strains of mice appear to be highly synergistic in tumor induction in the GVHR. The SJL/J virus is a powerful oncogenic agent. The C57BL/1 virus may be a helper virus to the SJL/J, but is a more powerful determinant of the antigenic composition of the induced tumors. This suggests that the virus of C57BL/1 mice, when activated, is capable of controlling the C57BL/1 genome. Because of the ease and rapidity of viral tumor induction, the SJL/J and C57BL/1 strains of mice, with their F1 hybrid, should be useful for further study of the mechanisms controlling induction of such tumors.

Blood ◽  
1964 ◽  
Vol 24 (6) ◽  
pp. 770-774 ◽  
Author(s):  
LUCIANO FIORE-DONATI ◽  
LUIGI CHIECO-BIANCHI ◽  
GIUSEPPE DE BENEDICTIS ◽  
GIUSEPPE TRIDENTE

Abstract Dissociated thymus cells are capable of initiating graft-versus-host reaction in (C3Hf/Gs x DBA/2)F1 hybrids only when derived from parental donors previously sensitized against the antigens of the other parental strain. The lower immunologic activity of thymus cells as compared with other lymphoid cells is presumably due to quantitative rather than qualitative differences in immunologically competent cells.


1966 ◽  
Vol 123 (1) ◽  
pp. 103-118 ◽  
Author(s):  
William L. Elkins

The graft versus host reaction (GVHR), which results from the injection of parental strain spleen cells beneath the kidney capsule of F1 hybrid rats, is transferable during its developmental phase into F1 hybrid hosts isogeneic with the primary host, but not into secondary hosts of the parental (donor) strain. Furthermore, the GVHR propagates but rarely in secondary hybrid hosts which are allogeneic with respect to the primary hosts, but which are also genetically tolerant of donor-type cells. These findings indicate that the donor cells not only initiate the GVHR but also maintain it by virtue of immunologically specific activity. Whole-body irradiation of (LBf)F1 and (LBN)F1 hosts 24 hours prior to the injection of parental (L) spleen cells results in inhibition of the subsequent GVHR to a degree commensurate with the radiation damage sustained by the lymphoid system of the host. Furthermore, propagation of transferred GVHRs did not occur if susceptible secondary hybrid hosts had been previously irradiated. These findings indicate that radiosensitive host cells play a continuing and essential role in the pathogenesis of the invasive-destructive lesion. It is concluded that the development of this lesion depends upon the continuous interaction of the specifically reactive donor-type cells with an immunologically non-specific population of host mononuclears.


1964 ◽  
Vol 119 (2) ◽  
pp. 211-224 ◽  
Author(s):  
R. Michael Blaese ◽  
Carlos Martinez ◽  
Robert A. Good

1. Adult (A x C57Bl/1)F1 hybrids regularly show runt disease when injected with adult spleen cells from A strain donors. This also occurs when A strain spleen cells are administered to adult C3H mice made tolerant of A strain tissue in the neonatal period. 2. Mice undergoing the graft versus host reaction fail to form antibodies to an intraperitoneal challenge of T2 bacteriophage. This phenomenon was observed well before any of the other overt signs of runting had occurred. Further, inhibition of antibody production to T2 phage by graft versus host reaction initiated at an interval following antigenic stimulation is demonstrated. 3. The basis for the immunologic incompetence of the host with respect to T2 phage is presumed to be the attack of immunologically competent donor cells on the lymphoid cells of the recipient. 4. The failure of the injected parent strain cells to respond to the antigen used may imply immunologic commitment of these cells.


1973 ◽  
Vol 137 (5) ◽  
pp. 1213-1225 ◽  
Author(s):  
Jan Klein ◽  
Jong M. Park

H-2 crossovers and their parental strains were arranged into 35 combinations in which the adult donor of spleen cells differed from the newborn recipient in the whole H-2 complex, or in three, two, or one region of the complex. A Simonsen splenomegaly assay was then used to test the contribution of the individual H-2 regions to the graft-versus-host reaction (GVHR). It was shown that the strongest GVHR was associated with the Ir region. Differences in the Ir region caused significant splenomegaly in spite of the fact that no antigens detectable by conventional serological methods have thus far been associated with this region. Differences in the K and D regions showed only a borderline effect on GVHR in spite of the fact that these regions code for most, if not all, of the antigens detectable by conventional serological and transplantation methods. The K region alone caused no stronger GVHR than the D legion alone; however, K + Ir region differences led to much stronger GVHR than D region differences. The Ss-Slp region also showed only a borderline effect on GVHR. Differences in two or more H-2 regions usually caused greater splenomegaly than differences in each of the regions separately. On the basis of these findings it is concluded that the strongest GVHR is caused by genes distinct from the known histocompatibility genes of the H-2 complex. It is speculated that the GVHR genes are identical with the mixed lymphocyte reaction (MLR) and Ir genes and that the product of these genes are receptors on the surface of the thymus-derived lymphocytes (T cells).


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