Accelerated age‐dependent decline in the T suppressor capacity of SJL mice

Abstract

Tolerance induction with rabbit gamma-globulin was employed as a probe for age-dependent changes in suppressor capacity of SJL lymphoid cells. The tolerant state was assessed by loss of cooperative capacity and by infectious tolerance. The supply of precursor cells was assessed by thymectomy and by treatment with colchicine and cyclophosphamide, which have been reported to eliminate suppressor cells. Thymectomy, 16-18 days before tolerance induction, did not affect antibody response or tolerance inducibility; thymectomy, 33 days before tolerance induction, reduced both antibody response and tolerance inducibility. Colchicine, injected together with aggregate-freed rabbit gamma-globulin, inhibited tolerance induction partially in 35-day-old mice and completely in 106-day-old mice. Colchicine, given to younger mice, thymectomized 17 days before tolerance induction, prevented tolerance induction completely. A low dose of cyclophosphamide interfered with tolerance induction in older, but not in younger mice. A high dose of cyclophosphamide interfered with tolerance induction in thymus cells of younger and older mice. After thymectomy, there was a much more profound interference of a low dose of cyclophosphamide with tolerance induction. Results were discussed in terms of an age-dependent decline of thymus progenitors and of peripheral progenitors of suppressor cells.

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.…”

“…BXSB/MpJ. and MRL/MpJ-lpr/lpr in ihe mechanism that led to resistance against tolerance [2,3,12,16,24]. In C57BL/6, loss of suppressor capacity occurred relatively slowly, and the apparent resistance against tolerance induction resulted from the reactivity of subpopulations of B cells.…”

“…31]. 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].…”

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

“…Next, we shall consider the loss of T-cell cooperative and infectious capacity and the relative sensitivity of the two assays. Finally, we shall examine our findings in terms of suppressor precursor pools and compare the magnitude of these pools in A/J mice with that found in SJL mice, reported elsewhere [6,7,20].…”

Nitric oxide production in SJL mice bearing the RcsX lymphoma: a model for in vivo toxicological evaluation of NO.

“…SJL mice were derived from the Swiss-Webster strain (15) and exhibit multiple immunological disorders, paraproteinemia (16), and myositis (A. H. Weller, S. A. Magliato, K. P. Bell, and N. L. Rosenberg, unpublished data). They are suspected of having defective suppressor T-cell function (17), and during the first year of life, spontaneously develop lymphomas arising in germinal lymphoid centers (15,18). The lymphomas are of B-cell lineage (19,20) and present an mouse mammary tumor virus long terminal repeat-derived superantigen on their surface.…”