The introduction of defned haptenic determinants into immunogenic carriers by Landsteiner (1) has provided a poweriul tool for the analysis of specific interactions between antigens and specific ceils in the immune response. Considerable evidence has been obtained demonstrating that cellular immune reactions to hapten-protein conjugates (delayed sensitivity [2-@ stimulation of DNA synthesis by antigen [7,8], and hapten-specific secondary responses [9-111) display a significant although variable degree of carrier specificity. Such carrier specificity of hapten-specific cellular reactions was initially interpreted to reflect the partial specificity of the antigen-binding receptors of specific cells for the carrier molecule (12-16), paralleling the demonstrated carrier specificity of anfi-hapten humoral antibodies (16)(17)(18).This interpretation of carrier function, however, is not able to explain several essential characteristics of hapten-specific immune responses:(a) The magnitude of the carrier specificity of cellular immune reactions cannot be easily explained by the relatively modest contribution, in energetic terms, of the carrier molecule to the specificity of most anti-hapten humoral antibodies (16-18):(b) Hapten conjugates of immunogenic molecules are required to elicit strong antihapten antibody responses; nonimmunogenic substances serve only poorly, or not at all, as carriers for haptens (19)(20)(21).(e) The induction of immunological unresponsiveness to the carrier molecule results in the partial or total suppression of the responses to haptens on the tolerated proteins (22)(23)(24)(25)(26)(27).If the specificity of serum antibody accurately expresses the specificity of the antigenbinding receptors present on the precursors of antibody forming cells, then these findings suggest the operation o[ an additional recognition mechanism for the carrier molecule. This interpretation would be strengthened if cooperation between carrier-specific and hapten-specific cells were found to be essential for the development of anti-hapten immune responses. According to this view, cells capable o[ reacting with carrier molecules should interact with the antigen be[ore anti-hapten antibody producing cells could be stimulated by hapten-protein conjugates.Mitchison (28) and Rajewsky et al. (29), have recently demonstrated such cooperation between carrier-specific cells and hapten-specific cells in anti-hapten secondary 261

The magnitude and heterogeneity of the immune response to dinitrophenylated bovine gamma globulin was measured in aged and young mice at a cellular level using an inhibition of plaque-forming cell assay. The primary and secondary responses of 24-mo-old mice were markedly depressed in magnitude and restricted in avidity for the DNP determinant when compared to 2-mo-old animals. Bacterial lipopolysaccharide given at the time of immunization increased the restriction in heterogeneity seen in 12- and 24-mo-old mice. Indirect PFCs were more severely depressed than direct PFCs in 24-mo-old mice. Syngeneic, lethally irradiated, 2-mo-old mice reconstituted with aged spleen cells exhibit the depressed and restricted response to DNP-BGG seen in old mice. When 10(8) young thymus cells were given together with old spleen cells the heterogeneity of the response was increased. When 2-mo- and 24-mo-old spleen cells were transferred together into young recipients the magnitude of the response to the young spleen cells markedly reduced. Thus, there appears to be a loss of thymic-helper cells and an increase in suppressor activity in aged animals.

No abstract

Transfer of lymphoid cells from strain-2 guinea pigs immunized to bovine gamma globulin into syngeneic recipients immunized with dinitrophenyl ovalbumin markedly enhances the secondary antidinitrophenyl response of the recipient to challenge with dinitrophenyl-bovine gamma globulin. This function of the carrier bovine gamma globulin-specific cells is resistant to irradiation with up to 5000 rads, although the capacity of the irradiated cell population to transfer immunologic memory for bovine gamma globulins or to be stimulated by antigen to synthesize DNA in vitro is abolished by this treatment.