Phenotypic and functional modulation of T cells in vivo by extrathymic T cells when T cells with MHC class II disparity were injected into athymic nude mice.
TCRhigh cells are generated by the mainstream of T cell differentiation in the thymus, whereas TCRint cells (or NK1.1+ T cells) are generated extrathymically in the liver and by an alternative intrathymic pathway. It is still unknown how these T cell populations interact in vivo with each other. To investigate the interaction of TCRint cells with TCRhigh cells, we used congenitally athymic nude (B6-nu/nu) mice which carry only TCRint cells in all immune organs. When TCRhigh cells from B6-C-H-2bm12 (bm12) mice (i.e. I-Abm12) were injected into B6-nu/nu mice (i.e. 1-Ab), the expanding T cell population was a mixture of TCRhigh cells of donor origin and TCRint cells of recipient origin. However, 9 Gy-irradiated nude mice permitted a full expansion of TCRhigh cells which expressed the IL-2Ralpha+beta+ phenotype, namely, they were at the most activated state. These mice died of acute graft-versus-host disease (GVHD) within 5 days. On the other hand, non-irradiated nude mice suppressed the expansion of TCRhigh cells of donor origin and such TCRhigh cells continued to have the IL-2Ralpha(+/-)beta+ phenotype. These mice could survive but showed signs of chronic GVHD thereafter. In both situations, CD4+alphabeta T cells expanded irrespective of donor or recipient origin. These results suggest that TCRint cells in the recipient mice possess a regulatory function in relation to donor TCRhigh cells; as a result, fully activated TCRhigh cells acquired the IL-2Ralpha+beta+ phenotype and injured the host, but TCRhigh cells suppressed in vivo remained as the IL-2Ralpha(+/-)beta+ phenotype and only partially injured the host.
Tomiyama
K
K
Department of Immunology, Niigata University School of Medicine, Japan.
Watanabe
H
H
Seki
S
S
Ito
M
M
Abo
T
T
D000818:Animals; D017252:CD3 Complex / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis; D018959:CD57 Antigens / Q000032:analysis; D002454:Cell Differentiation; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007165:Immunosuppression Therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
D017252:CD3 Complex; D019002:CD56 Antigen; D018959:CD57 Antigens; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2