Functional clonal deletion versus active suppression in transplantation tolerance induced by total-lymphoid irradiation

Journal Article · Thu Aug 01 04:00:00 EDT 1985 · Transplantation; (United States)

DOI:https://doi.org/10.1097/00007890-198508000-00019· OSTI ID:5019377

Morecki, S; Leshem, B; Weigensberg, M; Bar, S; Slavin, S

Transplantation tolerance and stable chimerism were established in adult mice conditioned with a short course of total-lymphoid irradiation (TLI) followed by infusion of 30 X 10(6) allogeneic bone marrow cells. Spleen cells of tolerant mice could not exert a proliferative or cytotoxic response against host-type cells in vitro and were unable to induce graft-versus-host reaction in secondary host-type recipients. The degree of suppression assessed by coculturing tolerant splenocytes in vitro in the one-way mixed lymphocyte reaction was quite variable--and, in some cases, was not at all demonstrable, although tolerance was clearly maintained. Suppression, when apparent, could not be ascribed to T lymphocytes. Suppressor cells were found to bind soybean agglutinin and could be separated from the nonsuppressive cells by means of this lectin. Dissociation of the suppressive population (SBA+ cells) from that which is normally alloreactive (SBA- cells) resulted in a suppressor cell-depleted fraction that was still unable to respond to host-type cells but regained reactivity to unrelated cells. Limiting dilution analysis of chimeric splenocytes revealed markedly reduced frequencies of cytotoxic T lymphocyte precursors (CTL-P) directed against host-type cells, as compared with normal splenocytes reacting against the same target cells. This difference was accentuated when these cells were sensitized to host-type target cells prior to plating in limiting dilution cultures. In 1:1 mixing experiments of normal and chimeric splenocytes, there was no evidence of any in vitro suppressive activity to account for hyporeactivity of chimeric cells against host-type cells. Thus, maintenance of TLI-induced tolerance seemed not to be mediated primarily through an active suppressor cell mechanism.

• Research Organization: Hadassah Univ. Hospital, Jerusalem, Israel
• OSTI ID: 5019377
• Journal Information: Transplantation; (United States), Journal Name: Transplantation; (United States) Vol. 2; ISSN TRPLA
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
BONE MARROW CELLS
CELL PROLIFERATION
CHIMERAS
CONNECTIVE TISSUE CELLS
GRAFT-HOST REACTION
IMMUNOSUPPRESSION
IN VITRO
INFUSION
INTAKE
IRRADIATION
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MATERIALS
MICE
MOSAICISM
PRECURSOR
RADIATION CHIMERAS
RODENTS
SOMATIC CELLS
SPLEEN CELLS
SURVIVAL TIME
TRANSPLANTS
VERTEBRATES