Increased production of Kurloff cells and accompanying lymphocyte subset changes in immunized guinea-pigs treated with cyclophosphamide and cyclosporin A.
We have used a panel of novel monoclonal antibodies to investigate the influence of cyclophosphamide (Cy) and cyclosporin A (CsA) on blood and spleen mononuclear cell populations in guinea-pigs immunized with ovalbumin (OVA) in complete Freund's adjuvant (CFA). Female animals received, on Day 0, 100 micrograms OVA/CFA in each hind footpad and were treated with either Cy (300 mg/kg i.p., Day -3) or CsA (25 mg/kg orally, daily from Day 0) or with both drugs. Two weeks later, mononuclear cell suspensions were prepared from blood and spleen. Immunocytochemical (alkaline phosphatase anti-alkaline phosphatase) analyses were performed using monoclonal antibodies directed against pan T cells, T-suppressor/cytotoxic (Ts/c) cells, a putative T-helper (Th) cell marker, B lymphocytes and to Ia antigen. Cy and CsA, particularly the former, caused depletion of T cells, although no striking differential effect of either drug was observed on the T-suppressor cell population. Cy caused a more severe depletion of B-cell numbers, whilst CsA selectively spared these cells. The number of Ia-positive mononuclear cells also decreased markedly in the blood of animals given either drug and in the spleens of those guinea-pigs given both Cy and CsA. In contrast, absolute numbers of Kurloff cells (mononuclear leucocytes unique to the guinea-pig and possessing a proteoglycan-containing inclusion body) were markedly increased in the blood and spleen of animals given Cy and CsA compared with animals given Cy or CsA alone. Phenotypic analysis revealed that the Kurloff cells bore the pan T-cell marker, (but neither the Ts/c nor Th subset markers) and were Ia positive. The model described provides an opportunity for further characterization of these cells, their function and of factors regulating their production.
Thomson
A W
AW
Department of Pathology, University of Aberdeen, U.K.
McPhee
C A
CA
Sewell
H F
HF
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D003520:Cyclophosphamide / Q000494:pharmacology*; D003524:Cyclosporins / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006168:Guinea Pigs; D007958:Leukocyte Count / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008214:Lymphocytes / Q000145:classification*; D010047:Ovalbumin / Q000276:immunology; D013154:Spleen / Q000276:immunology
D000954:Antigens, Surface; D003524:Cyclosporins; D003520:Cyclophosphamide; D010047:Ovalbumin