Sequential appearance of host-derived T cell subsets during differentiation in nude mice grafted with rat fetal thymus.
To elucidate the abnormality of T cell differentiation in nude mice grafted with rat fetal thymus that develop multiple-organ-localized autoimmune diseases, we examined sequential appearance of T cell subsets and expression of TCR genes in BALB/c nude mice after grafting with fetal F344 rat thymus. We observed progressive expression of TCR gamma/delta-alpha/beta genes in the lymph node (LN) cells from 8 to 12 wk after grafting. An appreciable number of CD4+ T cells but few CD8+ T cells were detected in the LN at 8 wk after grafting. CD8+ T cells increased slowly in number by 12 wk after grafting but remained at a low level in comparison with those in nude mice 12 wk after grafting with BALB/c thymus. In correlation with an increase in the number of T cells expressing TCR alpha/beta genes, alloreactivity as assessed by MLR was increased to a normal level. However, CTL activity against alloantigens remained at a low level in the LN cells at 12 wk. At this stage, organ-specific autoimmune diseases and a high level of anti-DNA autoantibodies were detected. In these mice host-reactive T cells such as V beta 3- or V beta 11-bearing T cells were virtually eliminated in the peripheral mature T cell pool, whereas T cells maturing in the fetal rat thymus significantly proliferated in response to donor-rat stimulator cells. These results suggest that the development of the autoimmune diseases may be ascribed to an impaired maturation of CD8+ T cells but not to failure in clonal elimination of host-reactive T cells in nude mice grafted with rat thymus.
Iwasaki
A
A
Department of Immunology, School of Medicine, Kyushu University, Fukuoka, Japan.
Yoshikai
Y
Y
Sakumoto
M
M
Himeno
K
K
Yuuki
H
H
Kumamoto
M
M
Sueishi
K
K
Nomoto
K
K
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology; D015152:Blotting, Northern; D002454:Cell Differentiation; D005434:Flow Cytometry; D015870:Gene Expression; D007111:Immunity, Cellular; D008198:Lymph Nodes / Q000502:physiology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology* / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013950:Thymus Gland / Q000637:transplantation*
D000974:Antibodies, Antinuclear; D000945:Antigens, Differentiation, T-Lymphocyte; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell