Heterogeneity of splenic natural suppressor cells induced in mice by treatment with cyclophosphamide.
Administration of high dose cyclophosphamide (CY, 200 mg/kg body weight) to adult mice induces transient, nonspecific suppressor activity in the spleen of treated animals. Characterization of the CY-induced natural suppressor (NS) cells which inhibit mixed lymphocyte reactions revealed a heterogeneous population of lymphocytes expressing the CD8 T cell marker and the B220 B cell marker, as well as cells bearing the granulocyte-monocyte marker CD11b. On a cell per cell basis the most potent of these suppressors were found to be positive for CD11b. Inhibitory activity was also detected in the CD8-, CD11b-, B220- compartment of CY-spleen, suggesting the presence of null NS cells. The fact that several phenotypically distinct cell populations contribute to the overall inhibitory effect of CY-spleen cells indicates that natural suppression defines an activity rather than a specific cell type. Interestingly, NS activity was observed to reside solely within the fraction of CY-spleen that is agglutinable with soybean agglutinin or wheat germ agglutinin, suggesting that expression of receptors for these plant lectins is a universal characteristic of CY-induced NS cells, regardless of their lineage. CY-spleen cell-mediated suppression of lymphoproliferative responses was found to be partially dependent on DNA synthesis and totally dependent on protein synthesis, but did not require cell-cell contact, indicating the production of soluble suppressor factor(s).
Department of Microbiology and Immunology, Dalhousie University, Halifax, N.S., Canada.
J C
JC
Brooks-Kaiser
L A
LA
Bourque
D W
DW
Hoskin
D000818:Animals; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000494:pharmacology*; D005434:Flow Cytometry; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D016685:Mitomycin / Q000494:pharmacology; D011691:Puromycin / Q000494:pharmacology; D013154:Spleen / Q000166:cytology* / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
D011691:Puromycin; D016685:Mitomycin; D003520:Cyclophosphamide