Effects of cyclosporin A on the splenic tissue of rats: a histomorphometric analysis

Histological studies demonstrated that long-term cyclosporin A treatment of nonantigenically challenged (untransplanted and unimmunized) Lewis rats markedly reduces the total percentage of splenic white pulp when compared to untreated control spleens (mean = 24 vs 34%, P less than 0.001). Direct measurements of periarteriolar sheaths and marginal zones demonstrated a marked reduction in size of these compartments in cyclosporin A-treated rats compared to untreated controls (P less than 0.001). In addition, there was a striking reduction in cellular density of the periarteriolar sheaths (P less than 0.001) and a minimal reduction in cellular density of the marginal zones (P less than 0.1) in the cyclosporin A-treated group when compared to untreated controls. There was no significant difference in total splenic size between the cyclosporin A-treated and the control groups, as indicated by total cross section measurements (mean = 33.3 vs 35.0, P less than 0.4). Qualitative observations of methyl green-pyroninophilic cells within and surrounding the marginal zones of the cyclosporin A-treated spleens revealed a much greater proportion of large pyroninophilic lymphocytes, which suggests that they are B immunoblasts. We conclude that long-term cyclosporin A treatment depletes splenic periarteriolar sheaths and marginal zones, compartments known to contain primary T lymphocytes, and induces an immunoblastic cell proliferation within the marginal zones and red pulp as well.