Generation of large granular lymphocytes and lymphocyte subset changes linked with cyclophosphamide-induced eosinophilia in rats--and the effects of ciclosporin.
Administration of cyclophosphamide (Cy: 150 mg/kg i.p.) to rats 48 h before immunization with a T-dependent antigen (ovalbumin) resulted in a striking absolute eosinophilia in blood, bone marrow, and secondary lymphoid organs after 10 to 14 days. This eosinophilia was preceded by a significant increase in the W3/25+/OX-8+ (T helper/inducer to T cytotoxic/suppressor) ratio in lymph nodes and spleen and accompanied by a pronounced rise in splenic OX-12+ (B cell) numbers. There was also a concomitant increase in cells with the morphology and immunophenotype (OX-8+, OX-19-) of large granular lymphocytes (LGL). It is suggested that the eosinophilia linked with the B lymphocytosis may be due to cell-derived soluble factors, including a possible equivalent of eosinophil differentiation factor (EDF = interleukin 5), which also has B-cell growth factor activity (BCGF II) in mice. Ciclosporin (CsA; 25 mg/kg/day per os) from the time of immunization, did not affect the incidence of W3/25+ cells in spleen or lymph nodes, but abrogated Cy-induced eosinophilia and reduced the extent of B-cell proliferation. In addition, CsA caused a further, marked increase in the incidence of OX-8+, OX-19-LGL within the spleen. The functional role(s) of these latter cells remains to be defined.
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology*; D003524:Cyclosporins / Q000494:pharmacology*; D004802:Eosinophilia / Q000139:chemically induced*; D007114:Immunization; D007694:Killer Cells, Natural / Q000187:drug effects*; D007958:Leukocyte Count; D008198:Lymph Nodes / Q000276:immunology; D008214:Lymphocytes / Q000145:classification / Q000187:drug effects*; D008222:Lymphokines / Q000096:biosynthesis; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects
D003524:Cyclosporins; D008222:Lymphokines; D003520:Cyclophosphamide