Genetics and strain distribution of concanavalin A-reactive Ly-2-, L3T4- peripheral precursors of autoreactive T cells

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Abstract
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 precursors 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.

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