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Splenic modifications induced by cyclophosphamide in C3H/He, nude, and "B" mice.

The spleen cell population of adult C3H/He mice injected with a single sublethal dose of cyclophosphamide (CY) has been analyzed. An initial phase of spleen atrophy is followed by a considerable hypertrophy, and a progressive return to normal. During the phase of spleen atrophy, both B and T cell compartments are depleted, as estimated by the percentages of cells killed by anti-Thy 1-2 and anti-Ig antisera plus complement. During the stage of regeneration, the percentage of Ig + cells increases rapidly, and at the peak of splenomegaly, the percentage of Ig + cells is high whereas almost no Thy 1-2 + cells are detectable. Progresively, the spleen cell content returns to the original values. In thymo-deprived mice (nude mice and B mice) the percentage of null cells increases during the stage of regeneration, and B mice develop a large number of Ig +-bearing cells. Histologic examination shows that follicles (B-dependent areas) disappear 1 to 2 days before periarteriolar sheaths (T-dependent areas). At the peak of splenomegaly the architecture of the spleen is destroyed, and the interstitial tissue is composed of a dense and uniform layer of lymphoid cells. Progressively, the architecture returns to normal. In nude mice, the disappearance of follicles, and the appearance of a homogenous layer of lymphocytes has been observed. When analyzed for their pattern of electrophoretic mobilities (E.M.), spleen cells from untreated mice reveal two peaks of E.M. 0.80 and 1.15 micron x s-1 x V-1 x cm-1. After CY treatment, during the step of splenic hypertrophy, these two peaks disappear, and a single peak of intermediate mobility appears. In T-deprived mice, a single peak of the same mobility is detected at this stage. The nature and origin of cells which appear during the phase of regeneration are unclear, but their appearance in T-deprived mice argues against thymo dependence. These spleen cells have the ability to suppress the response of normal spleen lymphocytes to T and B cell mitogens.