Journal of Experimental Medicine, Vol 157, 1867-1884, Copyright © 1983 by Rockefeller University Press
T cell regulation of B cell activation. I-A-restricted T suppressor cells inhibit the major histocompatibility complex-restricted interactions of T helper cells with B cells and accessory cells
Y Asano and RJ Hodes
The present studies were carried out to characterize the cellular
interactions involved in the activation and function of the antigen-
specific and antigen-nonspecific T suppressor (Ts) cells that regulate the
IgG responses of Lyb-5-B cells. The in vitro activation of both Lyt- 1+2-
antigen-nonspecific Ts cells and Lyt-1-2+ antigen-specific Ts cells was
shown to require the interaction of accessory cells and antigen-primed T
cells. It was further demonstrated that this interaction was major
histocompatibility complex (MHC)-restricted in that T cell recognition of
I-A-encoded determinants on accessory cells was required for Ts cell
activation. The activation of antigen-primed (A X B)F1 T cells with antigen
in the presence of parentA or parentB accessory cells resulted,
respectively, in the generation of parentA- restricted or
parentB-restricted Ts cells. ParentA-restricted F1 Ts cells suppressed the
responses generated by (A X B)F1 T helper (Th) cells cooperating with
parentA (B + accessory) cells but did not suppress responses by the same (A
X B)F1 Th cell population cooperating with parentB (B + accessory) cells.
Neither parentA-restricted Ts cells alone nor parentB-restricted Ts cells
alone suppressed the responses of (A X B)F1 (B + accessory) cells, whereas
a mixture of these two Ts cell populations was able to significantly
suppress the responses of F1 (B + accessory) cells. In contrast, responses
of (A X B)F1 leads to parentA Th cells (restricted to recognizing parentA
but not parentB MHC determinants on F1 cells) and (A X B)F1 (B + accessory)
cells was suppressed by parentA-restricted Ts cells but not by
parentB-restricted Ts cells. Collectively these findings suggest that the
Ts cell populations characterized here do not function by directly
inhibiting the activity of Th cells, B cells or accessory cells of a given
MHC genotype, but rather that they appear to function through a unique
mechanism involving highly specific inhibition of the interaction between
MHC-restricted Th cells and the (B + accessory) cells required for these
responses.
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