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Scripps Clinic and Research Foundation, Department of Immunopathology, La Jolla, California 92037
Abstract
In a previous report, it was shown that spleen cells from mice made tolerant to human 
-globulin (HGG)5 could specifically inhibit the immune response of normal spleen cells after adoptive transfer to lethally irradiated recipients. However, that report also showed that the suppressive activity was only transiently associated with tolerant spleen cell populations. It was concluded from those experiments that while suppressive activity could be demonstrated in tolerant spleen cells under certain conditions, such activity was not obligatory for the maintenance of the tolerant state. The experiments presented here were performed to determine the nature of the effector cell(s) and the target cell(s) involved in this system of suppression of the immune response. Treatment of cells from tolerant animals with anti-thymocyte serum and complement to remove thymus-derived (T) cells completely abrogated suppressive activity. Removal of adherent cells from tolerant spleen cells by passage over glass wool columns resulted in partial loss of the suppression. The inhibitory activity of the suppressor cells was resistant to 900 R irradiation regardless of whether the tolerant spleen cells were irradiated before or after adoptive transfer.
The cellular target(s) for the suppressor cells was examined by using lipopolysaccharide (LPS) as an alternative source of helper activity for the response to HGG. LPS, injected at the time of the initial antigenic challenge of mice that had been reconstituted with tolerant and normal spleen cells, prevented the expression of suppression against bone marrow-derived (B) cells. However, when LPS was presented only at the time of the secondary antigenic challenge, it was unable to overcome suppression of the immune response of reconstituted recipients. Thus, LPS could produce a state where the B cells were resistant to suppression, but LPS could not rescue the responsiveness of B cells once the cells in the reconstituted recipient had been suppressed. In addition, the immune responses to both the hapten dinitrophenol (DNP) and the carrier (HGG) were suppressed when recipients of tolerant and normal spleen cells were challenged with DNP 6HGG. This indicates that T helper cells are also a target for suppression.
The results presented in this paper are discussed in relation to a possible mechanism of suppression which proposes that suppressive activity represents the induction of tolerance in immunologically competent cells by HGG which is closely associated with the tolerant spleen cells.
Footnotes
1 This is Publication No. 1133 from the Departments of Immunology, Scripps Clinic and Research Foundation, La Jolla, California. The work was supported by U. S. Public Health Service Grant AI-07007, U. S. Public Health Service Training Grant GM-00683-15, Atomic Energy Administration Contract E (04-3)-410, and American Cancer Society Grant IM-42F.
5 Abbreviations used in this paper: HGG, human -globulin; LPS, lipopolysaccharide; DNP, dinitrophenol; DHGG, deaggregated HGG; DEAE, diethylaminoethyl; BSA, bovine serum albumin; i.p. intraperitoneal; i.v. intravenous; PFC, plaque-forming cells; GRBC, goat red blood cells; AHGG, aggregated HGG.
2 Recipient of National Institutes of Health Fellowship Award AI-01023.
3 Recipient of National Institutes of Health Fellowship Award AI-05012.
4 Recipient of U. S. Public Health Service Research Career Award 5-K6-GM-6936.
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