| First Author | Giese T | Year | 1995 |
| Journal | J Immunol | Volume | 154 |
| Issue | 10 | Pages | 4986-95 |
| PubMed ID | 7537297 | Mgi Jnum | J:25105 |
| Mgi Id | MGI:72818 | Doi | 10.4049/jimmunol.154.10.4986 |
| Citation | Giese T, et al. (1995) In CD8+ T cell-deficient lpr/lpr mice, CD4+B220+ and CD4+B220- T cells replace B220+ double-negative T cells as the predominant populations in enlarged lymph nodes. J Immunol 154(10):4986-95 |
| abstractText | Mice homozygous for lpr or gld develop autoimmunity and progressive lymphoproliferative disease characterized by the accumulation of two unusual populations of B220+ TCR-alpha beta+ T cells, a predominant CD4-CD8- double-negative (DN) subset and a minor CD4dull+ subset. B220+ DN T cells appear to be derived from negatively selected thymocytes, but their immediate precursors have not been identified conclusively, and their relationship to CD4+B220+ T cells is unclear. Our previous studies of lpr and gld mice treated chronically with anti-CD8 mAb provided evidence that the majority of B220+ DN T cells are unrelated to CD4+B220+ T cells and may be descended from peripheral thymus-derived CD8+ T cells. To investigate the contributions of MHC class I-selected thymus-derived T cells to the production of B220+ DN T cells and to the accumulation of CD4+ T cell subsets, we studied C3H-lpr and -gld mice rendered deficient in CD8+ T cells by the introduction of disrupted beta 2-microglobulin (beta 2-m) genes. These CD8+ T cell-deficient mice developed massively enlarged lymph nodes, in which CD4+B220+ T cells and CD4+ T cells replaced B220+ DN T cells as the dominant T cell subsets. As a population, the CD4+B220+ T cells were depleted of autoreactive populations specific for endogenous retroviral superantigens and were enriched for V beta 8.3+ T cells. The deficiency of CD8+ T cells in beta 2-m(-/-)-lpr mice had no effects on the accumulation of primed CD4+ T cells or autoreactive B cells. The selective reduction in B220+ DN T cells and corresponding accumulation of CD4+B220+ T cells in beta 2-m(-/-)-lpr mice provide strong evidence that 1) the majority of B220+ DN T cells are unrelated to CD4+ T cells and their development and/or accumulation is dependent on MHC class I expression; and 2) CD4+B220+ T cells are a remarkably similar, but separate, lineage of cells that develop independently of thymus-derived CD8+ T cells and class I MHC expression. |
