Sensitization of T-cell receptor-alpha beta+ T cells recovered from long-term T-cell receptor downmodulation.
Although the survival of fully allogeneic skin grafts was prominently prolonged by adult thymectomy in anti-T-cell receptor-alpha beta monoclonal antibody (TCR-alpha beta mAb)-treated mice compared with that of non-adult thymectomized (ATX) mice, the skin allografts were eventually rejected. In the anti-TCR-alpha beta mAb-treated ATX mice, as shown in the present study, most of TCR-alpha beta+ cells were promptly activated on day 2 and then rapidly disappeared by day 7, but some TCR-alpha beta- Thy-1+ cells remained at that time. These TCR-alpha beta- Thy-1+ cells which have downmodulated their TCR-alpha beta expression may be refractory to depletion events by the mAb treatment. Although these downmodulated T cells re-expressed their TCR-alpha beta on day 50, they could not respond to stimuli via TCR such as TCR cross-linking or alloantigens. However, they recovered the reactivity to donor antigens on day 85. These results indicate that the downmodulated T cells by anti-TCR-alpha beta mAb treatment are long-lived and re-express their TCR-alpha beta at a late stage to be sensitized to donor antigen, which suggests that additional regimens may be required to get permanent, or very long-term, graft acceptance.
Omoto
K
K
Department of Immunology, Kyushu University, Fukuoka, Japan.
Kong
Y Y
YY
Nomoto
K
K
Umesue
M
M
Murakami
Y
Y
Eto
M
M
Nomoto
K
K
D000818:Animals; D016525:Antigenic Modulation; D015536:Down-Regulation; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D016219:Immunotherapy, Adoptive; D051379:Mice; D008815:Mice, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013934:Thymectomy; D013997:Time Factors; D014184:Transplantation, Homologous
D016693:Receptors, Antigen, T-Cell, alpha-beta