SPECIFIC, TRANSIENT SUPPRESSION OF IMMUNE-RESPONSE BY HGG TOLERANT SPLEEN-CELLS .2. EFFECTOR CELLS AND TARGET-CELLS

  • 1 January 1976
    • journal article
    • research article
    • Vol. 117  (4) , 1152-1158
Abstract
It was previously shown that spleen cells from mice made tolerant to human .gamma.-globulin (HGG) could specifically inhibit the immune response of normal spleen cells after adoptive transfer to lethally irradiated recipients. The suppressive activity was only transiently associated with tolerant spleen cell populations. 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 present experiments 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 [Echerichia coli] 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 were reconstituted with tolerant and normal spleen cells, prevented the expression of suppression against bone marrow-derived (B) cells. When LPS were 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 were suppressed. The immune responses to the hapten dinitrophenol (DNP) and the carrier (HGG) were suppressed when recipients of tolerant and normal spleen cells were challenged with DNP6HGG. T helper cells are probably also a target for suppression. Suppressive activity probably represents the induction of tolerance in immunologically competent cells by HGG which is closely associated with the tolerant spleen cells.

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