Mononuclear phagocytes from patients with active systemic lupus erythematosus down-regulate the specific in vitro reactivity of autologous lymphocytes to double-stranded DNA.
Peripheral mononuclear cells (MNC) from patients with systemic lupus erythematosus (SLE) are hyporesponsive in vitro. In order to study the role of mononuclear phagocytes (m phag) in regulating the in vitro responses of autologous lymphocytes, the MNC from 16 SLE patients (eight active, eight inactive) and 14 healthy controls were stimulated in vitro with PHA or dsDNA. The proliferative response to PHA was tested by 3H-thymidine incorporation on day 4 and the response to dsDNA using a specific haemolytic plaque assay. Indomethacin, an inhibitor of prostaglandin (PG) synthesis by m phag, was added into the cultures to test the presence of suppressive m phag acting through a PG-mediated pathway. Indomethacin augmented the proliferative response to PHA in active SLE cultures and not in inactive SLE or controls. In six of 13 SLE cultures, dsDNA totally or partly suppressed anti-dsDNA plaque-forming cell (PFC) generation. Indomethacin restored or enhanced the PFC response to dsDNA in active SLE and not in inactive SLE or controls. M phag depletion by plastic adherence prevented the effects of indomethacin. These results show that m phage exerting a suppressive activity on PHA-induced lymphocyte proliferation and on anti-dsDNA antibody production are found in cultures from active SLE and generally not in inactive SLE or healthy individuals. PHA being primarily a T-cell stimulator, the m phag suppressive activity observed in PHA-stimulated cultures is exerted on T cells. On the other hand, in two active SLE cultures depleted of T cells by OKT3 antibody, indomethacin still could enhance the PFC response to dsDNA, showing that in vitro suppressive m phag can act directly on B cells from patients with active SLE.
Weill
B J
BJ
Laboratoire d'Immunologie, Faculte Cochin, Paris, France.
Renoux
M L
ML
D000328:Adult; D000368:Aged; D000921:Antibody-Producing Cells / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000276:immunology*; D005260:Female; D006462:Hemolytic Plaque Technique; D006801:Humans; D007108:Immune Tolerance; D007213:Indomethacin / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010586:Phagocytes / Q000276:immunology*
D004247:DNA; D007213:Indomethacin