What signals macrophages to signal lymphocytes?

A study was made of the control of the immunogenic function of antigen fed macrophages. We demonstrated that treatment of macrophages with antigen plus the Ig associated tetrapeptide tuftsin (Thr-Lys-Pro-Art), augmented dramatically the generation of specific initiator T-lymphocytes. Testing the effects of various synthetic analogs of tuftsin we concluded that the Pro-Arg sequence dominates the activation of the immunogenic effect of antigen-fed macrophages. Since these sequences appear in many polypeptide hormones, we suggest that the different amino acid sequences of the different hormones are recognized by the receptors of the various target cells on which they act. Yet they all may generate the intracellular signal, resulting in the activation of the programmed state of the cell, via the Pro-Arg sequences. Studies of spleen cells from tolerant animals indicated that they prevent the generation of ITL by antigen fed macrophages. We then demonstrated that spleen cells from high zone tolerant animals contain suppressor T-cells which suppress the antigen presenting macrophages. In fact, they act as cytotoxic cells on the tolerogen presenting macrophages. We suggested that such suppressors are anti-altered self killers, recognizing macrophage cell surface components 'altered' by the tolerogen. We then indicated that the differentiation of the immunogenic capacity of macrophages is controlled by a sub-set of short lived, yet cortisone resistant, T lymphocytes.