| First Author | Sobel ES | Year | 1995 |
| Journal | Clin Immunol Immunopathol | Volume | 74 |
| Issue | 2 | Pages | 177-84 |
| PubMed ID | 7828372 | Mgi Jnum | J:22559 |
| Mgi Id | MGI:70419 | Doi | 10.1006/clin.1995.1026 |
| Citation | Sobel ES, et al. (1995) The abnormal lpr double-negative T cell fails to proliferate in vivo. Clin Immunol Immunopathol 74(2):177-84 |
| abstractText | Mice homozygous for the autosomal recessive gene lpr develop marked lymphadenopathy and a systemic autoimmune disease resembling human systemic lupus erythematosus. The enlarged nodes are dominated by T cells with an unusual surface phenotype: dull Thy-1+, dull CD3+, CD4-, CD8-, B220+ (double-negative T cells or DNTs). Despite their massive accumulation in vivo, these cells fail to proliferate in response to conventional T-cell mitogens in vitro. The identification of the lpr mutation as a defect in the Fas apoptosis receptor gene suggests that DNT accumulation may result from abnormal persistence rather than overproliferation. To test in vivo whether DNTs persist abnormally or have a capacity to differentiate into single-positive T cells, we have performed cell transfer experiments between congenic strains of lpr and +/+ mice differentially marked by expression of the Ly-1 or Thy-1 alleles. Although transferred lpr lymph node cells were mostly DNTs at the time of injection, most recovered cells of donor origin were single positive, particularly CD8+, at all time points after transfer. Furthermore, transfer of purified DNTs resulted in recovery of relatively few cells of donor origin. Transfer of lpr T cells enriched for CD8 expression confirmed the preferential survival of this subset. Thus, DNTs are a surprisingly transient population and have little capacity for transformation to single positives. This would suggest that DNTs are constantly being renewed, perhaps from CD4+ and CD8+ precursors. |
