AN ASSAY OF GRAFT-HOST INTERACTIONS ACROSS STRONG AND WEAK HISTOCOMPATIBILITY BARRIERS IN MICE

Journal Article · Wed May 01 04:00:00 EDT 1963 · J. Exptl. Med.

DOI:https://doi.org/10.1084/jem.117.5.863· OSTI ID:4661846

Miller, J; Pierce, J C; Martinez, C; Good, R A

Studies were undertaken on the assumption that grafthost interactions when both donor and recipient are capable of immune responses may be quite unlike the unidirectional graft-vs-host reaction. A new criterion of graft-host interactions is presented, based on the early finding of mononuclear cell infiltrates of donor origin in the livers of recipient mice after administration of homologous lymphoreticular cells. In the evaluation of donor cell reactivity these infiltrates are consistent in appearance as compared with spleen enlargement, a more variable and complex response. This model is sensitive enough to detect such graft-host interactions between strains with a common H-2 histocompatibility locus, and can detect differences in the degree of reactivity of strains to each other when injected reciprocally. When cell products or cells unable to proliferate were injected, i.e., sonically disrupted or lethally x irradiated cells, no liver infiltrates were seen. In addition, an infiltrate incidence of 17% was obtained both when F/sub 1/(A x C57B1/1) hybrid spleen cells were injected into A recipients, or when spleen cells from thymectomized A strain donors were injected into C57B1/1 (B/sub 1/) recipients. By contrast, A cells injected into thymectomized or xirradiated B/sub 1/ recipients produced liver infiltrates in all the animals. Thus, it appears that these infiltrates, present after the injection of immunologically responsive donor cells into unresponsive hosts, were of donor origin. Spleen cells from lethally x-irradiated A strain animals were injected into B/sub 1/ recipients, and AB/sub 1/ F/sub 1/ hybrid cells into A recipients. In both cases only a slightly greater spleen enlargement was obtained. When cells from thymectomized A strain donors were injected into B/sub 1/ recipients, a splenomegaly significantly greater than that of the former groups was observed. There was also a significant splenomegaly when A spleen cells were injected into neonatally thymectomized B/sub 1/ animals. In the x-irradiated B/sub 1/ recipients of A spleen cells, spleen wt decreased, but was significantly greater than those found in lethally x-irradiated but noninjected controls. Thus, the quality or quantity of injected antigen may have played a role in inducing spleen enlargement in the recipients. In addition, splenomegaly may have been due to specific immune responses on the part of the donor cells against the recipient. Spleen enlargement seems to stem from a more complex combination of causes, while the infiltrative lesions of the liver appear to be only proliferating donor cells. Graft-host interactions were also demonstrated in the DBA/2 and Balb/C strains isogenic at the H-2 histocompatibility locus. The lag observed in the appearance of liver infiltrates when DBA/2 spleen cells were injected into the Balb/C host, as compared with the reciprocal arrangement, parallels the degree of facility of reciprocal tolerance induction in adult animals of these strains. Tolerance to Balb/C skin grafts is achieved in adult DBA/2 animals by a single intravenous injection of only 100 million Balb/C adult spleen cells. However, multiple intravenous injections of DBA/2 cells, or a single injection of DBA/2 cells following sublethal x irradiation, were needed to achieve tolerance in Balb/C recipients. (H.H.D.)

• Research Organization: Univ. of Minnesota, Minneapolis
• NSA Number: NSA-17-027122
• OSTI ID: 4661846
• Journal Information: J. Exptl. Med., Journal Name: J. Exptl. Med. Vol. Vol: 117
• Country of Publication: Country unknown/Code not available
• Language: English

Related Subjects

AGE
ANIMAL CELLS
BIOLOGY AND MEDICINE
IMMUNITY
LETHAL DOSE
LIVER
LYMPH SYSTEM
MICE
REGENERATION
SPLEEN
SPLENOMEGALY
SURGERY
THYMUS
TRANSPLANTS
ULTRASONICS
VOLUME
X RADIATION