The involvement of human tumor necrosis factors-alpha and -beta in the mixed lymphocyte reaction.
The influence of recombinant human TNF-alpha and -beta (rHuTNF-alpha and -beta) in a human mixed lymphocyte reaction (MLR) was investigated. The addition of 1000 U/ml of either cytokine at the initiation of culture caused up to a sixfold increase in [3H]thymidine incorporation by responder cells. Furthermore, it was found that endogenous HuTNF-alpha is produced after allogeneic cell interaction and can be detected in the MLR supernatant within 1 h of culture initiation. The results also show that, in the absence of exogenous HuTNF-alpha, antibodies to rHuTNF-alpha can cause a significant inhibition of the MLR. These observations indicate the importance of TNF-alpha in allogeneic cell interaction and raise considerations for the use of antibodies, or other antagonists, to TNF-alpha as regulators of disease states associated with cell-mediated immune reactions.
Shalaby
M R
MR
Department of Pharmacological Sciences, Genentech, Inc., South San Francisco, CA 94080.
Espevik
T
T
Rice
G C
GC
Ammann
A J
AJ
Figari
I S
IS
Ranges
G E
GE
Palladino
M A
MA
D000818:Animals; D000906:Antibodies / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000502:physiology; D007376:Interleukin-2 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D011817:Rabbits; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*
D000906:Antibodies; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha