Anti-CD3 induced thymocyte apoptosis in vivo require the antibody Fc domain.
We have earlier found that explanted thymic epithelial cells (TEC) can produce glucocorticoid (GC) activity in vitro and that the GC receptor (GR) antagonist RU486 partially inhibit thymic apoptosis induced by the anti-CD3 monoclonal antibodies (MoAb) 2C11, both in vivo and in new-born thymic organ cultures. To explain the inhibitory effect of RU486 in this system we have now investigated the importance of the 2C11 Fc as this MoAb bind with high affinity to cellular FcR. We have found both that whole 2C11 MoAb can bind to explanted TEC in vitro and that F(ab)'2 fragments from this MoAb loose this ability, in addition with the capacity to induce thymic apoptosis in vivo. We interpret our results to indicate that the injected 2C11 MoAb may establish a close contact between GC producing, FcR positive TEC cells and CD3 positive thymocytes and thereby subject the later to high paracrine GC concentrations and subsequent induction of apoptosis.
Xue
Y
Y
Microbiology and Tumorbiology Center (MTC); Immunopathology Laboratory, Karolinska Institute, S-171 77 Stockholm, Sweden.
Castanos-Velez
E
E
Biberfeld
P
P
Jondal
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007128:Immunoglobulin Fragments / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011961:Receptors, Fc / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; C111990:CD3fos-F(ab')2; D007141:Immunoglobulin Fc Fragments; D007128:Immunoglobulin Fragments; D011961:Receptors, Fc