Cyclophosphamide treatment antagonizes the in vitro development of Mycobacterium lepraemurium-induced suppressor cell precursors.
The in vitro-inducible maturation of splenic suppressor cell precursors detected during the early phase of Mycobacterium lepraemurium infection can be abrogated when a high dose of cyclophosphamide (Cy) is inoculated to infected mice 2 days before assay. The drug does not act directly on adherent suppressor cell precursors, but rather inhibits their activation by a non-adherent cell subset whose phenotype has not yet been elucidated. It was established by flow cytometry analyses, that despite a marked increase in the total number of splenic non-adherent cells following M. lepraemurium infection, the effect of Cy on Ia+, Thy-1+, CD4+ and CD8+ cells in infected mice was comparable to that observed in normal controls. It was not possible to determine the duration of the inhibiting effect of Cy on non-adherent regulatory cells, because the drug was itself inducing suppressor cells from 7 days after inoculation. By the time spleen cell suspensions were totally free of Cy-induced suppressor cells, infection-dependent suppressor cell precursors were once again detected, indicating that Cy treatment did not prevent their in vivo accumulation. Therefore, even though M. lepraemurium-induced adherent suppressor cell precursors are themselves fully resistant to Cy, their development is transiently abrogated by the drug, most probably through the impairment of a non-adherent cell subset regulating their maturation.
Gosselin
D
D
Immunology Research Center, Institut Armand-Frappier, Université du Québec, Laval, Canada.
Turcotte
R
R
Lemieux
S
S
D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D016131:Lymphocyte Subsets / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D009164:Mycobacterium Infections / Q000276:immunology*; D009167:Mycobacterium lepraemurium; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000502:physiology
D003520:Cyclophosphamide