Simpson Ma

Development of suppressor t cells by antilymphocyte serum treatment in mice.

Administration of rabbit anti-mouse lymphocyte serum (ALS) in mice results in the development of suppressor cells which can be detected by coculture mixed lymphocyte culture experiments. The putative suppressor cells inhibit nonspecifically the proliferative response as well as generation of cytotoxicity of normal responder cells. Suppressor activity is dose dependent and is not attributable to cell crowding, shifting of peak activity, or release of cell-bound ALS. Additional antigenic stimulation by skin allografting in ALS-treated mice shifts the specificity of suppressor cells from nonspecific to specific for skin donor alloantigen. ALS-induced suppressor cells are Lyt-1+2- T cells while suppressor cells present in ALS-treated, skin allograft-bearing mice are Lyt-1-2+ T cells. Both types of suppressor cells appear to bear I-J determinants. The possible mechanisms of suppressor cell induction by ALS and skin allografting are discussed.

Studies On The Mechanism Of Action Of Rabbit Anti-mouse Thymocyte Serum

Treatment of B6AF1 (C57BL/6 × A/Jax) mice with either rabbit anti-mouse thymocyte serum (ATS) or with both ATS and sheep red blood cells (SRBCs) resulted in the generation of splenic suppressor cells within 5 days. Suppressor activity was determined by injecting secondary syngeneic recipients with both donor cells and SRBCs. Five days later the SRBCs hemolytic effect of their spleen cells was determined. Suppressor cells were found in either whole spleen or enriched T cell suspensions from mice treated with ATS and SRBCs and in only enriched T cell suspensions from mice treated with ATS alone. These results support the possibility that ATS induces a population of suppressor cells and that these cells may be responsible in part for the immune suppression noted after treatment with ATS.

Binding of antihuman globulin by exfoliated renal tubular cells following kidney transplantation.

Exfoliated renal tubular epithelial cells (RTCs) from kidney allograft recipients may bind antibody against human globular proteins. Urine from sixty consecutive transplant recipients was studied in the first month following transplantation to relate this binding to the clinical course and rejection. The spun, washed sediment was incubated with fluoresceinated goat antihuman globulin and examined under light and fluorescent microscopy for fluoresceinated RTCs. Of 28 patients who were never positive, 27 manifested no clinical rejection episodes. Of 22 total rejection episodes, 21 were preceded by the appearance of fluorescent RTCs. Five patients in this group did not revert to negative in this test, and all went on to loss of graft from acute rejection. Of 46 patients who were discharged from the hospital with negative RTCs, only four were readmitted within one month for treatment of rejection. In contrast, of the 11 patients who were positive at the time of discharge, 10 were readmitted in the first month. Graft survival was only 55% (6/11) in this latter group as compared with 91% (42/46) in the former. There were 11 patients with transiently positive tests who did not warrant a clinical diagnosis of rejection. In no case of acute tubular necrosis (ATN) alone or in obstructive uropathy was the assay positive. However, in some cases, in which the ATN merged imperceptibly into rejection, the RTCs started to fluoresce well in advance of the clinical suspicion of rejection. Information obtained from this examination may be used to assess the cause of renal failure in the early posttransplant period and to differentiate rejection from ATN and obstruction. This phenomenon of fluorescent RTCs may be an early manifestation of an immunological change occurring in a cell that is targeted by the host for rejection.