Activation and suppression of graft-vs-host reactions by cyclophosphamide

We have investigated the effects of a single injection of cyclophosphamide (CY) on the graft-vs-host (GVH) reactivity of spleen cells from BALB/c mice. Six days after CY injection, spleen cells showed a broad range of reactivity when tested for their capacity to produce splenomegaly in young F1 hybrid recipients. Eight and 10 days after CY treatment, their capacity to produce GVH splenomegaly was markedly reduced. We also investigated the effects of untreated and CY-treated BALB/c spleen cells on the local GVH reaction that occurs when BALB/c lymph node pieces are grafted onto F1 host kidneys. Untreated BALB/c spleen cells augmented the local GVH reaction, whereas day 8 CY-treated BALB/c spleen cells reduced the local reaction. Day 6 CY-treated BALB/c spleen cells marginally reduced the local response and elicited considerable host splenomegaly. Day 6 CY-treated F1 hybrid spleen cells stimulated the local GVH reaction and did not produce splenomegaly. We interpret our results to indicate that CY treatment leads to a) the appearance on day 6 of a BALB/c cell population with increased GVH reactivity, b) the emergence of a suppressive mechanism by day 8 that results in reduced GVH reactivity, and c) an alteration at day 6 in F1 lymphoid cell antigenicity that enables these cells to stimulate an ongoing GVH reaction. We discuss our results in terms of the similar effects that CY has on GVH-reactive and autoreactive cell populations, and examine the possibility that the mechanisms that underlie GVH reactivity and autoreactivity are similar in that both involve imbalances of immunoregulatory cell populations..