Mechanisms involved in graft-versus-host disease induced by the disparity of minor histocompatibility M1s antigens.
In this study we investigated which type of T cells: high T-cell receptor (TCRhigh, cells of thymic origin) or intermediate TCR (TCRint, cells of extrathymic origin), expanded in the liver and other organs, resulting in the induction of graft-versus-host disease (GVHD) with minor lymphocyte stimulating (M1s) disparity. When 6.5 Gy-irradiated BALB/c (H-2d M1s-1b2a) mice were injected with interleukin-2 receptor beta-chain(-) (IL-2Rbeta(-)) CD3high cells purified from the spleen of B10.D2 (H-2d M1s-1b2b) mice, IL-2Rbeta(+)CD3high cells expanded in the liver and other organs of recipient mice. The majority of these cells were found to be IL-2Ralpha(-)Mel-14(-)CD4(+)Vbeta3(+) in GVHD mice. The CDR3 region in their TCR-alphabeta (i.e. N-Dbeta-N) was polyclonal, although there were skewed usages of Vbeta3 and Jbeta2.4. The majority of cells were confirmed to be of donor origin by the individual discrimination method, namely, they originated from isolated IL-2Rbeta(-)CD3high cells. Interestingly, these T cells lacked cytotoxicity against both a natural killer (NK)-sensitive target and thymocytes with M1s disparity and nondisparity. Another important finding was that activated granulocytes expanded at generalized sites in GVHD mice. The present results raise the possibility that M1s disparity is mainly recognized by TCRhigh cells with unique properties but that direct effector cells that induce GVHD might not be such T cells but rather accompanied granulocytes.
Kawamura
T
T
Department of Immunology, Niigata University School of Medicine, Japan.
Kawachi
Y
Y
Kuwano
Y
Y
Sugahara
S
S
Weerasinghe
A
A
Kosaka
T
T
Seki
S
S
Abo
T
T
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D006098:Granulocytes / Q000276:immunology; D008099:Liver / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016747:Minor Lymphocyte Stimulatory Antigens; D008969:Molecular Sequence Data; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000637:transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology
D017931:DNA Primers; D016747:Minor Lymphocyte Stimulatory Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA