Suppressor Cells and their Precursors in A/J Mice, Tolerant to Heterologous Gamma Globulin

Abstract

The role of suppressor cells and of their precursors was examined in A/J mice, immunized or tolerized-immunized with rabbit gamma globulin. Antibody response and tolerance were assessed by antigen elimination, followed by an indirect plaque-forming assay. Reconstitution experiments were performed to estimate loss of cooperative capacity in thymus and spleen cells. Infectious tolerance was examined by reconstitution with mixtures of spleen or thymus cells of normal and tolerant donors. Infectious tolerance could not be detected after neonatally induced tolerance. It could be detected when tolerance was induced 11-16 days after birth. Under these circumstances, loss of cooperative capacity and increased capacity for infectious tolerance occurred rapidly over the first 2 days and reached completion by the 10th-20th day after administration of tolerogen. Thymectomy, after tolerance induction, resulted in relative recovery of responsiveness of spleen cells and loss of capacity for infectious tolerance. Pretreatment with cyclophosphamide resulted in a less profound state of unresponsiveness and in the disappearance of the capacity for infectious tolerance. Simultaneous treatment with tolerogen and colchicine also resulted in a less profound state of tolerance. This effect of colchicine was more profound when a low dose of tolerogen was used or when animals were thymectomized before administration of tolerogen and colchicine.

Mechanisms Involved in Age‐dependent Decline of Immune Responsiveness and Apparent Resistance against Tolerance Induction in C57BL/6 Mice

“…A relatively small agedependent loss in cooperative capacity occurred between the 63rd and 245th day of age. Having concluded from earlier experiments with other strains that colchicine could reduce the clfcci of suppressor cells [24,26] and having shown the effect in this study in terms of immune 0.2</»<0.3 C57BL/6 mice were toleri/ed by the injection of aggregate-freed RGG (0.2 mg/g body weight) at various ages. The mice were immunized with alum-DNP-RGG 7 and 17 days after tolerance induction, inlraperitoneally.…”

“…Animals receiving colchicine at ages at which the decline of suppressor cells was relatively feeble showed no significant changes in the degree of tolerance inducibility [26]. Thus (see Table 111), since colchicine had a substantial effect on the antibody response of 245-day-old but not of 63-day-old animals, we interpret these data to indicate a loss of suppressor cells, probably in (urn a reflection of a loss of precursors of these specific suppressor ceils [26,31]. Thus, the age-dependent decline in helper capacity, suggested in the data of Tahic II.…”

“…Our earlier experiments on tolerance inducibility suggested that the effects of colchicine was greatest when ihere was a marked decline in the peripheral precursors of suppressor cells [24]. Animals receiving colchicine at ages at which the decline of suppressor cells was relatively feeble showed no significant changes in the degree of tolerance inducibility [26]. Thus (see Table 111), since colchicine had a substantial effect on the antibody response of 245-day-old but not of 63-day-old animals, we interpret these data to indicate a loss of suppressor cells, probably in (urn a reflection of a loss of precursors of these specific suppressor ceils [26,31].…”

Age-Dependent Changes in Antigenic Promotion, A Th-2 Type of Activity

“…It has also been shown that in vivo responses require an effective interac tion between Th-1 and B cells, whereas Th-2 influences the quality of the antibody re sponse by augmenting certain aspects of it [Janeway et al, 1980], We have observed age-dependent changes in Th-2 type of helper capacity in SJL mice, where they are first demonstrable when the animal is 4-5 weeks old and increase rapidly up to the age of 10-15 weeks [Matsuzawa and Cinader, 1982a, b]. In this paper, we propose to examine changes in A/J and C57BL/6 mice; several other aspects of their age-related changes have been studied in the past [Crowle et al, 1981;Teague et al, 1970;Rodeyct al., 1971;Adler et al, 1978;Nakano and Cinader, 1980a, b;Slut man, 1974;Meredith et al, 1979;Amagai et al, 1982],…”