Inhibition of lymphocyte IL2-receptor expression by factor VIII concentrate: a possible cause of immunosuppression in haemophiliacs.
Factor VIII concentrate inhibits T-cell function in vitro and in vivo. The mechanisms underlying the phenomenon were investigated. Factor VIII concentrate has a direct effect on lymphocytes, uninfluenced by haemophilic monocyte dysfunction, since it inhibited lymphocyte transformation with phorbol myristate acetate, a reaction unaffected by monocyte depletion. Inhibition of lymphocyte transformation by factor VIII concentrate is not corrected by the addition of exogenous IL2, suggesting that it does not inhibit lymphocyte function by suppression of IL2 secretion alone. Factor VIII concentrate causes profound inhibition of IL2-receptor expression (CD25); with an 89% reduction in CD25-positive CD4 cells and a 50% reduction in CD25-antigen molecules per cell. CD8 lymphocytes are similarly affected. Smaller reductions in CD71 and HLA-DR expression are also observed. Down modulation of CD25-antigen may explain the reduced IL2 secretion observed by others, and may be an important cause of immunodeficiency in HIV-seronegative haemophiliacs.
Hay
C R
CR
Department of Haematology, University of Liverpool.
McEvoy
P
P
Duggan-Keen
M
M
D015703:Antigens, CD / Q000032:analysis; D004306:Dose-Response Relationship, Immunologic; D005169:Factor VIII / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis; D006467:Hemophilia A / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000032:analysis*
D015703:Antigens, CD; D006684:HLA-DR Antigens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D005169:Factor VIII