T cells from patients successfully treated with OKT3 do not react with the T-cell receptor antibody.
The mechanism of OKT3 therapy is complex and may include depletion of circulating CD3 cells, modulation of the CD3 molecule, and/or functional inactivation of T cells. Although the absolute number of circulating CD3 cells in OKT3-treated patients is used to monitor therapy, many laboratories assign CD3 numbers based on reactivity with OKT3. These CD3 numbers could be artificially low since the epitope recognized by OKT3 may already be occupied. Using a monoclonal antibody against a different CD3 epitope, we detected CD3 expression on T lymphocytes from 18/18 OKT3-treated patients. Nonetheless, OKT3 therapy in these patients was clinically successful, suggesting that monitoring patients solely for CD3 is uninformative. Since CD3 is associated with the T-cell receptor (TcR), we also evaluated alpha-TcR-1, a monoclonal antibody which detects a conformational determinant of the CD3/TcR alpha/beta complex, and found that less than 1% of the CD3 cells from OKT3-treated patients reacted. Furthermore, these cells were unresponsive to allogeneic stimulation. However, when patient cells were cultured overnight in the absence of OKT3, both alpha-TcR 1 binding and responsiveness to allogeneic stimulation became detectable. Thus, the monitoring of patients treated with OKT3 can be more informative if lymphocytes are tested for reactivity with alpha-TcR-1 and an alpha-CD3 antibody other than OKT3.
Gebel
H M
HM
Department of Immunology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612.
Lebeck
L K
LK
Jensik
S C
SC
Webster
K
K
Bray
R A
RA
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology; D017252:CD3 Complex; D000939:Epitopes; D005455:Fluorescent Antibody Technique; D006801:Humans; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D015166:Monitoring, Immunologic; D016853:Muromonab-CD3; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D000939:Epitopes; D016853:Muromonab-CD3; D011948:Receptors, Antigen, T-Cell