The abnormal lpr double-negative T cell fails to proliferate in vivo.
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.
Sobel
E S
ES
Department of Medicine, University of Florida, Gainesville 32610.
Kakkanaiah
V N
VN
Rapoport
R G
RG
Eisenberg
R A
RA
Cohen
P L
PL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D005434:Flow Cytometry; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D008198:Lymph Nodes / Q000166:cytology; D008206:Lymphatic Diseases / Q000235:genetics / Q000276:immunology*; D017710:Lymphocyte Transfusion; D051379:Mice; D008817:Mice, Mutant Strains; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D013934:Thymectomy