T-cell receptor-bearing cells from athymic nude rats respond to alloantigen in vitro but are defective in vivo.
T-like cells from congenitally athymic nude rats of the PVG (RT1c) strain were characterized both phenotypically and functionally. There was an age-dependent increase in the number of alpha beta TcR+CD3+ cells in the lymph nodes, spleen and thoracic duct of nude rats. These cells, which comprised up to 25% of lymph node cells in animals of 8-12 months in age, were also CD3+CD5+Thy-1.1-. The expression of CD4 and CD8 on T-like cells was mutually exclusive. Approximately 30% of the CD4+ cells expressed CD45RB and 50% of the TcR+ cells expressed RT6. B-cell-depleted TcR+ cells from nude animals gave proliferative responses to mitogenic lectins or immobilized anti-CD3 antibody. T-like cells showed comparable alloreactivity to their euthymic counterparts in mixed lymphocyte reactions (MLR) against three different MHC haplotypes and to lymphocytes of a congenic strain differing only in MHC-encoded products. Monoclonal antibodies (mAb) to CD4, MHC class II, alpha beta TcR and CD3 blocked the MLR. However, T-like cells failed to induce rejection of skin allografts of the same MHC haplotypes when adoptively transferred to athymic nude hosts and were unable to mount a normal graft-versus-host (GVH) response. These results indicate that lymphocytes may rearrange and express a functional TcR in the absence of a thymus, but that the thymic microenvironment is essential for T cells to acquire full in vivo function.
Sarawar
S R
SR
Department of Cell & Structural Biology, Manchester University Medical School, U.K.
Yang
C P
CP
Bell
E B
EB
D000375:Aging / Q000276:immunology; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D002454:Cell Differentiation; D002455:Cell Division / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D006087:Graft vs Host Reaction / Q000276:immunology; D007519:Isoantigens / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008934:Mitogens / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D011923:Rats, Nude; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D000954:Antigens, Surface; D007519:Isoantigens; D008934:Mitogens; D011948:Receptors, Antigen, T-Cell