Activation of human T cells in vivo following treatment of transplant recipients with OKT3.
Sequential lymph node biopsies were obtained prior to and following OKT3 administration in 10 organ transplant recipients to determine whether activation of human T cells occurs in vivo during OKT3 administration. Within 2 hr after injection, OKT3 can be detected coating LN T cells, and LN T cells also demonstrate enhanced proliferation in vitro in the presence of recombinant interleukin-2 (rIL-2). Interleukin-2 receptor (IL-2R) is expressed on post-OKT3 LN T cells within 48 hr following administration of OKT3. In addition, when placed in a mixed lymphocyte reaction, post-OKT3 LN cells also demonstrate enhanced proliferation. This is the first direct demonstration of in vivo activation of human T cells by OKT3. These data support the hypothesis that T lymphocyte activation and concomitant production of lymphokines are responsible for the side effects associated with OKT3 treatment. Immune activation and possible enhancement of anti-donor MHC alloreactivity may have significant implications for anti-CD3 and anti-TCR monoclonal antibody therapy in clinical organ transplantation and for enhancement of the immune response in cancer patients.
Ellenhorn
J D
JD
Ben May Institute, Department of Pathology, University of Chicago Pritzker School of Medicine, Illinois.
Woodle
E S
ES
Ghobreal
I
I
Thistlethwaite
J R
JR
Bluestone
J A
JA
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008875:Middle Aged; D016377:Organ Transplantation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007140:Immunoglobulin Fab Fragments; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins