The Journal of Immunology, Vol 141, Issue 9 3022-3028, Copyright © 1988 by American Association of Immunologists
The selection of effector T cell phenotype by contrasuppression modulates susceptibility to autoimmune injury
CJ Kelly, H Mok and EG Neilson
Renal Electrolyte Section, University of Pennsylvania School of Medicine, Philadelphia 19104.
The genetic susceptibility to murine alpha TBM disease is a dominant trait
that maps to H-2K. In previous studies we have shown that the critical
difference between susceptible (SJL) and nonsusceptible (B10.S(8R] mice is
the phenotype of the tubular Ag-specific effector T cells (TDTH). In SJL
mice, these TDTH are Lyt-2+, whereas in B10.S(8R) mice the TDTH are L3T4+.
These phenotypic differences have an important functional correlate: Lyt-2+
TDTH are nephritogenic, whereas L3T4+ TDTH are typically not nephritogenic.
Both mouse strains have the potential to differentiate both L3T4+ and
Lyt-2+ TDTH. The preferential selection of a single TDTH phenotype in each
is the result of differential T cell regulation. In the present studies, we
have examined the contribution of suppressor and contrasuppressor T cells
in the regulation of TDTH phenotype selection. Our studies show that in
both SJL and B10.(8R) mice, after exposure to Ag, a suppressor T cell
subpopulation functions to inhibit the nephritogenic Lyt-2+ TDTH. In SJL,
but not B10.S(8R) mice, this suppression is counterbalanced by Lyt-2+,
Vicia Villosa lectin-adherent T cells. Such contrasuppressor function is
mediated through a T cell-derived soluble protein (TcsF), which is
Ag-binding and recognized by alpha I-JS antisera. This functional TcsF
activity maps, as does susceptibility to disease, to H-2K. In the presence
of genetically compatible TcsF, the TDTH phenotype in nonsusceptible mice
switches to that of susceptible mice. These Lyt-2+ TDTH from nonsusceptible
mice are fully capable of inducing tubulointerstitial nephritis following
adoptive transfer. Our studies describe a new role for Tcs cells and
augment our understanding of their etiopathogenetic role in autoimmunity.
