Enhancement of sheep erythrocyte (SRBC)-induced pleurisy in non-sensitized mice by cyclophosphamide: demonstration of natural cell-mediated immune reactivity to SRBC.

Intrapleural injection of 2 x 10(8) sheep erythrocytes (SRBC) into normal C57BL/6N (B6) mice produced a low but significant exudate leucocyte reaction, which was delayed in onset and mononuclear cell dominant. However, administration of 20-200 mg/kg cyclophosphamide (CY) in mice induced a dose-dependent enhancement of this reaction. In contrast, erythrocytes of syngeneic and allogeneic mice, rats, guinea-pigs rabbits and humans showed no or slight enhancement in CY-treated B6 mice. Maximal enhancement was observed on day 6 after CY treatment, but the reactions fell on day 7 and gradually decreased thereafter. B6 mice from specific pathogenfree colonies also showed strong reactions on day 6 after CY treatment. B6 mice demonstrated the highest reactions and C3H/He (C3H) mice were intermediate, while BALB/c mice showed very low responses. F1 hybrid (BALB/c x B6) mice showed an intermediate response as compared with the parent strains. The enhanced reactions reached their peak at 24 hr after SRBC injection and mainly consisted of macrophages and polymorphs. The enhancement could be successfully transferred to naive syngeneic mice by viable spleen cells from CY-treated mice but not by sera. The mediator cells could not bind to plastic petri dishes or a nylon-wool column, and were sensitive to anti-Thy-1.2 + C treatment . These results thus indicated that the enhancement was induced by the cell-mediated immune (CMI) mechanisms. The appearance of natural CMI reactivity to SRBC, and its role in relation to immunological reactions is discussed.