MODE OF ACTION OF THYMUS DERIVED (T) SUPPRESSOR AND AMPLIFIER CELLS

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The prior in vivo depletion of CD4+ T cells resulted in a significant decrease in the magnitude of the antibody response to several bacterial polysaccharide antigens, not know to require CD4+ helper T cells to initiate antibody production. Such suppression appears to be mediated by the inhibitory effects exerted by remaining CD8+ suppressor T cells (Ts); their effects become dominant in the absence of CD4+ amplifier T cells (Ta) that act in a positive and opposing manner to drive immune B cells to proliferate further in response to antigen. Treatment with various recombinant lymphokines (e.g., IL-2, IL-4, IL-5, but not IL-6) increased the expression of Ts activity in vivo; thus, Ts activity is effected greatly by lymphokines that influence the activation and/or expansion of Ts. Also, Ts, once activated, acquire a cell surface receptor and/or possess a biochemical pathway that is extremely sensitive to being blocked or inactivated by bacterial monophosphoryl lipid A (MPL). Such inactivation appears to be restricted to the expression of Ts activity since treatment with the same or larger amounts of MPL has no adverse effect on the expression of several other T cell functions examined.