Cyclophosphamide-induced eosinophilia in the rat: concomitant changes in T-cell subsets, B cells and large granular...

Cyclophosphamide (Cy) treatment (150 mg/kg) of Sprague-Dawley rats 48 hr before immunization with a T-dependent antigen, ovalbumin (OVA), resulted in striking bone marrow, blood and tissue eosinophilia, maximal at 14 days and concurrent with profound lymphopenia. This phenomenon has been tentatively attributed to selective elimination by Cy of T-suppressor cells. In this study, T-cell subsets, B cells and monocytes/macrophages were enumerated following alkaline phosphatase-anti-alkaline phosphatase (APAAP) staining of mononuclear cells isolated from lymphoid tissues of rats exhibiting eosinophilia. In lymph nodes, a significant increase in the A3/25+:OX-8+ ratio compared with normal was maintained from Day 7 to Day 14; in the spleen, however, this effect was no longer apparent by Day 14, due to the emergence of a population of OX-8+, OX-19- large granular lymphocytes. A seven-fold rise in splenic B-cell numbers (OX-12+) between Day 7 and Day 14 coincided with the eosinophilia. These findings are consistent with the potentiated production of TH-cell derived soluble factors affecting eosinophil production and differentiation, including possibly a rat equivalent of eosinophil differentiation factor, which in the mouse has been reported to have B-cell growth factor activity linked with eosinophilia.