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R H Wander

Publications and source records attributed to R H Wander.

5 recordsLinked to original sources

Host treatment with cyclophosphamide elicits transient changes in graft-versus-host reactivity of donor cells.

We have investigated the effects of a single injection of cyclophosphamide (CY) in F1 host mice. One day after CY treatment, F1 host mice show increased susceptibility to graft-versus-host (GVH)-reactive parental strain spleen cells when measured by the popliteal lymph node (PLN) enlargement assay. F1 host mice challenged with parental strain cells 7 days after CY treatment show decreased PLN enlargement as compared with CY-untreated F1 hosts receiving parental strain cells. The PLN reactivity of normal F1 spleen cells injected into F1 hosts pretreated with CY was also measured. F1 spleen cells elicited marked PLN enlargement when injected into F1 hosts that were treated with CY 1 day previously. By day 7 after CY treatment of F1 hosts, F1 cells no longer produced significant PLN enlargement as compared to untreated F1 hosts receiving F1 cells. We discuss these results in terms of the possibility that CY initiates changes in host antigenicity that can lead both to an increase in responsiveness of GVH-reactive cells and to susceptibility to attack by syngeneic cells.

Animals↗

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..

Animals↗