CD3 antibody-induced IL-10 in renal allograft recipients: an in vivo and in vitro analysis.
BACKGROUND
The first administration of CD3 monoclonal antibodies, such as anti-human CD3 (OKT3), induces a massive release of several cytokines, including tumor necrosis factor alpha (TNF-alpha), interferon (IFN)-gamma, interleukin (IL)-2, IL-3, IL-6, and granulocyte-macrophage colony-stimulating factor.


METHODS
Cytokine levels in patient's sera were measured by specific ELISA. In vitro cultures were performed using OKT3-stimulated peripheral blood mononuclear cells and/or whole blood from patients and normal controls.


RESULTS
Here we describe that OKT3 administration to human renal allograft recipients also leads to a significant release of IL-10. Contrasting with most OKT3-induced cytokines, such as TNF-alpha whose release is transient, IL-10 levels show a more progressive increase, they peak only by 4-8 hr after the first OKT3 injection and persist longer. Thus, significant IL-10 levels are still detectable at the time of the second and the third OKT3 injection. Administration of corticosteroids, 1 hr before the first OKT3 injection, significantly reduced both TNF-alpha and IL-10 release. Experiments were performed to evaluate the source(s) of IL-10 and its (their) influence on the initial T-cell activation. When stimulated in culture with soluble OKT3, the production of IL-10 was dependent on the cooperation between T lymphocytes and monocytes. It is important that, as assessed through the use of a specific neutralizing antibody, the endogenous IL-10 produced in the co-culture system exerted a negative feed-back on the release of the other pro-inflammatory CD3-induced cytokines, which was reproducible.


CONCLUSIONS
These results are supportive of a major role of IL-10 in the down-modulation of the OKT3-triggered T-cell activation cascade.
Herbelin
A
A
Association Claude Bernard and Service de Transplantation Renale, Hôpital Necker, Paris, France.
Abramowicz
D
D
de Groote
D
D
Naret
C
C
Kreis
H
H
Bach
J F
JF
Goldman
M
M
Chatenoud
L
L
D017252:CD3 Complex / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D016030:Kidney Transplantation; D008214:Lymphocytes / Q000378:metabolism; D008775:Methylprednisolone / Q000627:therapeutic use; D009000:Monocytes / Q000378:metabolism; D016853:Muromonab-CD3 / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012016:Reference Values; D012189:Retrospective Studies
D017252:CD3 Complex; D016207:Cytokines; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D011994:Recombinant Proteins; D016753:Interleukin-10; D008775:Methylprednisolone