Jc. Brookskaiser et al., HETEROGENEITY OF SPLENIC NATURAL SUPPRESSOR CELLS INDUCED IN MICE BY TREATMENT WITH CYCLOPHOSPHAMIDE, Immunopharmacology, 25(2), 1993, pp. 117-129
Administration of high dose cyclophosphamide (CY, 200 mg/kg body weigh
t) to adult mice induces transient, nonspecific suppressor activity in
the spleen of treated animals. Characterization of the CY-induced nat
ural suppressor (NS) cells which inhibit mixed lymphocyte reactions re
vealed a heterogenous population of lymphocytes expressing the CD8 T c
ell marker and the B220 B cell marker, as well as cells bearing the gr
anulocyte-monocyte marker CD11b. On a cell per cell basis the most pot
ent of these suppressors were found to be positive for CD11b. Inhibito
ry activity was also detected in the CD8-, CD11b-, B220- compartment o
f CY-spleen, suggesting the presence of null NS cells. The fact that s
everal phenotypically distinct cell populations contribute to the over
all inhibitory effect of CY-spleen cells indicates that natural suppre
ssion defines an activity rather than a specific cell type. Interestin
gly, NS activity was observed to reside solely within the fraction of
CY-spleen that is agglutinable with soybean agglutinin or wheat germ a
gglutinin, suggesting that expression of receptors for these plant lec
tins is a universal characteristic of CY-induced NS cells, regardless
of their lineage. CY-spleen cell-mediated suppression of lymphoprolife
rative responses was found to be partially dependent on DNA synthesis
and totally dependent on protein synthesis, but did not require cell-c
ell contact, indicating the production of soluble suppressor factor(s)
.