Alloactivation induced during mixed-lymphocyte reaction provokes release of tumor necrosis factor alpha and interleukin 6 by macrophages and primes them to lipopolysaccharides.
We tested various factors affecting the production of the CKs IL-6 and TNF-alpha during in vitro alloactivation induced by MLR. Different MLR combinations involving familial and unrelated pairs were evaluated. In family studies, MLRs involving pairs of HLA-identical siblings (n = 6) were characterized by IL-6 and TNF-alpha secretion comparable to the one of autologous controls, in marked contrast with HLA-different combinations (n = 6). These displayed a strong and early (day 3) release of both CKs. In combinations of unrelated individuals involving HLA-A, -B, -C-different but -DR, -DQ-identical pairs (n = 3), low CK release was observed. Addition of LPS (1 micrograms/ml) considerably increased production of IL-6 and TNF-alpha. Clear discrimination of MHC class II differences required a 24-hour preculture followed by addition of LPS for 4 hours, a time relationship compatible with a priming phenomenon due to alloactivation. We conclude that MHC class II alloactivation not only provokes IL-6 and TNF-alpha secretion, but also primes macrophages to LPS so that the production of these CKs is markedly increased and occurs much earlier after LPS addition.
Toungouz
M
M
Department of Immunology and Transfusion, Erasme Hospital, University Clinics of Brussels, Belgium.
Denys
C H
CH
De Groote
D
D
Andrien
M E
ME
Dupont
E C
EC
D016207:Cytokines / Q000378:metabolism*; D006680:HLA Antigens / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D006680:HLA Antigens; D015850:Interleukin-6; D007519:Isoantigens; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha