Journal of Experimental Medicine, Vol 150, 676-692, Copyright © 1979 by Rockefeller University Press
Suppressor T-cell mechanisms in contact sensitivity. III. Apparent non- major histocompatibility complex restriction is a result of multiple sets of major histocompatibility complex-specific suppressor T cells induced by syngeneic 2,4-dinitrophenyl-modified lymphoid cells
SD Miller
This report has examined the mechanisms by which major histocompatibility
complex (MHC) non-restricted suppressor T cells (Ts), induced by the i.v.
injection of 2,4-dinitropheny (DNP)-modified, syngeneic lymphoid cells
(DNP-LC), suppress the passive transfer of contact sensitivity mediated by
syngeneic and allogeneic immune delayed hypersensitivity T cells (TDH). In
terms of suppression of syngeneic TDH, it was found that the suppressive
action of the Ts was only blocked by pretreatment with soluble syngeneic
DNP-LC membrane preparations. Monomeric DNP-lysine, polymeric DNP-protein
conjugates, and syngeneic TNP-LC membranes did not inhibit Ts function.
Further experiments showed that inhibition of syngeneic suppression could
be achieved by DNP-modified-membrane preparations that were only H-2D-
region compatible with the Ts donor. Thus, Ts antigen receptors in this
system specifically recognize DNP-modified H-2D-region determinants. In
contrast, it was found that pretreatment os syninduced Ts with syngeneic
DNP-LC membranes did not inhibit the ability to suppress allogeneic TDH.
However, pretreatment of Ts with DNP-allogeneic membranes which were
H-2D-end compatible to the allogeneic target TDH eliminated their ability
to suppress the specific allogeneic TDH, leaving intact suppression of
syngeneic or third party TDH. It is proposed that perturbation of the
immune system by i.v. injection of syngeneic NDP-LC leads to the induction
of a polyclonal wave of DNP- specific Ts activity. Some members of this set
of Ts recognize DNP-self MHC determinants with moderate affinity and are
thus specifically inhibited after pretreatment with those DNP-self
determinants. Other members of this set display receptors which cross-react
with high affinity with DNP-allogeneic determinants and thus suppress
allogeneic TDH cells. These allosuppressive clones can thus be specifically
inhibited only by pretreatment with DNP-LC membranes, MHC-compatible with
the target TDH. The data are discussed in terms of current models of T-cell
cross-reactivity and T-cell-receptor recognition.
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