The effect of anti-lymphocyte serum on subpopulations of blood and tissue leucocytes: possible supplementary mechanisms for suppression of rejection and the development of opportunistic infections.
Xenogeneic anti-lymphocyte serum (ALS) remains a major reagent for immunosuppression in clinical practice, but mechanisms of action and risks of opportunistic infection have not been considered in the context of innate immunity and its role in immune responsiveness. Rabbit anti rat ALS was administered intraperitoneally. Blood was taken for flow cytometry to establish absolute counts of leucocyte subsets. Tissues were harvested for immunohistology to evaluate interstitial dendritic cells and tissue macrophages. At day 2 of ALS therapy, T cells are completely depleted, as anticipated. B cells are undiminished and form approximately 90% of blood leucocytes. Monocytes and natural killer (NK) cells are substantially (approximately 80%), but not completely, depleted, and there is a trend for diminished numbers of putative dendritic cells. Neither interstitial dendritic cells nor tissue macrophages in heart are affected. The results at day 7 were very similar to day 2. Substantial depletion of blood monocytes and NK cells might attenuate the innate immune system, and represent a possible supplementary mechanism (in addition to T cell depletion) for suppression of rejection. It might be of particular importance in reducing defences against infections. Monitoring these parameters could be of clinical value.
Geissler
Ina
I
Department of Clinical Sciences, Guy's, King's and St Thomas' School of Medicine, The Rayne Institute, King's Denmark Hill Campus, London, UK.
Sawyer
Greta J
GJ
Dong
Xuebin
X
Kandil
Hala
H
Davies
Edward T
ET
Fabre
John W
JW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001772:Blood Cell Count; D002469:Cell Separation; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D016027:Heart Transplantation / Q000009:adverse effects / Q000379:methods; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000378:metabolism; D009894:Opportunistic Infections / Q000517:prevention & control; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew; D013045:Species Specificity; D013997:Time Factors; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents