Genetics and strain distribution of concanavalin A-reactive Ly-2-, L3T4- peripheral precursors of autoreactive T cells.
Cytotoxic treatment of BALB/c cells from different peripheral lymphoid tissues by a cocktail of monoclonal antibodies against Thy-1, Ly-1, L3T4 and Ly-2 differentiation markers (anti-T cocktail) plus complement eliminates all mature T lymphocytes. Yet a population of dull Thy-1+, Ly-1-, L3T4-, Ly-2-, corresponding to about 1% of the initial population, can be detected by flow cytometry which proliferate under concanavalin A stimulation. These anti-T killing-resistant cells (TKR) were previously shown to be capable of differentiating in culture into class II-restricted autoreactive T helper cells. We demonstrate here that such cells can be detected in mice of BALB/c and DBA/2 genetic background but are absent in C57BL/6 and B10 animals. The presence of TKR cells is dominant in (BALB/c x C57BL/6)F1 hybrids and genetically controlled by two genes which are neither H-2 nor Igh linked. TKR cells are also detected in young NZB mice but disappear with the development of the systemic autoimmune disease in old animals. Thy-1+, L3T4-, Ly-2- cells from MRL lpr/lpr mice also respond to concanavalin A but are removed by the anti-T treatment. Altogether, arguments are presented suggesting that TKR cells represent a particular subset of double-negative peripheral T cells which may correspond to autoreactive T cell recursors that would escape the thymic selection. We postulate that these cells are present in all mouse strains but their susceptibility to killing by anti-Thy-1 antibodies differs depending on background genes.
Morisset
J
J
Laboratorie d'Immunodifférenciation, Institut Jacques Monod, CNRS-Université Paris, France.
Trannoy
E
E
De Talance
A
A
Spinella
S
S
Debré
P
P
Godet
P
P
Seman
M
M
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000950:Antigens, Ly / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000145:classification* / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008221:Lymphoid Tissue / Q000166:cytology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification*
D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D003208:Concanavalin A