Chronic graft-versus-host disease-like autoimmune disorders spontaneously occurred in rats with neonatal thymus atrophy

Abstract

We earlier reported that the human T cell leukemia virus type-1 pX gene transduced into rat thymic epithelial cells had an impact on biology of the cells. We report here that FWpX rats born by mating of F344 transgenic rats expressing the pX gene without tissue specificity with nontransgenic Wistar rats developed disorders, including atrophy of the thymus, lymphocytopenia, and inflammatory cell infiltration into multiple organs, similar to events in chronic graft-vs.-host disease (GVHD). Vanishment of thymic epithelial cells especially in the cortex and marked depletion of CD4 CD8 doublepositive thymocytes were evident in the neonatal thymus in these rats. The relative abundance of CD8 compared to CD4 T cells may be related to dominant infiltration of CD8 T cells into the affected organs. Additionally, adoptive transfer of FW-pX splenocytes could induce lymphocytic infiltration into sublethally irradiated wild-type syngeneic recipients. Analysis of the expression level of the Foxp3 gene in peripheral blood mononuclear cells revealed that the numbers of immunoregulatory T cells were less in FW-pX rats than in wild-type rats. The collective evidence suggested that the FWpX rats spontaneously developed chronic GVHD-like autoimmune diseases, following abortive differentiation of T cells in the thymus in early days of the newborn. This rat model may shed light on the pathogenesis of chronic GVHD and also other systemic autoimmune diseases, the etiology of which is unknown.

CD4+/CD8+ macrophages infiltrating at inflammatory sites: a population of monocytes/macrophages with a cytotoxic phenotype

“…5 These rats also displayed a compensatory increase in the number of peripheral myeloid cells. To characterize immunophenotypic alterations in their peripheral blood mononuclear cells (PBMCs), we performed 2-color FCM analysis using PBMCs isolated from 6-week-old FW-pX and age-matched control FW-wt rats ( Figure 1).…”

“…5 In these rats (hereafter referred to as FW-pX rats), the HTLV-I pX transgene induced neonatal apoptosis of the thymic epithelial cells, resulting in lymphocytopenia accompanied by compensatory expansion of peripheral myeloid cells, production of autoreactive T cells, and subsequent development of chronic GVHD-like autoimmune diseases.…”

MHC Class I-Like MILL Molecules Are β2-Microglobulin-Associated, GPI-Anchored Glycoproteins That Do Not Require TAP for Cell Surface Expression

“…For immunostaining, frozen sections prepared from 3-day-old, 10-day-old, and 6-wk-old male BALB/c mice were fixed using cold acetone for 5 min, washed with PBS, stained by the standard method (23), and then mounted in fluorescent mounting medium (DakoCytomation). Immunofluorescence was detected using a fluorescence microscope (ECLIPSE E600; Nikon).…”