This paper describes a 2-year experiment on the flux with aging in A/Jax female mice of Arthus and tuberculin-type delayed hypersensitivities to chicken conalbumin antigen, of delayed hypersensitivity to methylated human serum albumin antigen, of anamnestic responses for these phenomena, and of a low-dose tolerance. The mice began to lose ability to develop delayed hypersensitivity at 15–18 months of age, or 0.6–0.7 mean life span. They retained ability to develop Arthus hypersensitivity, general anamnestic responsiveness, a capacity to develop low-dose tolerance preventing primary induction of delayed hypersensitivity and, once sensitized, the ability to express delayed hypersensitivity reactions well into senescence ( > 0.8 mean life span). These findings agree generally with most others on age-related flux of immunologic responses in mice and man, that cell-mediated responses are shorter-lived than humoral responses, and that induction (primary responsiveness) is much more affected than reaction or anamnesis (secondary responsiveness). Retention with aging of a capacity to develop tolerance, apparently not previously studied, could be important in explaining flagging primary responsiveness, because this (i.e. induction) is what such tolerance suppresses. Thus, certain unanticipated aspects of the experiment reported here suggest that accumulated exposure to food antigens may have contributed to age-related (i.e. time-related) decline of immunologic responses by progressive induction of such tolerance. The simple experimental model described here should be useful for investigating this possibility and the interplay of positive and negative immunologic responses with particular relevance to understanding such effects in aging human beings, since it studies natural changes in whole mice but with greater control, speed and dissectability that could ever be possible in man.

Aging A/Jax female mice were compared with young controls for abilities throughout life to make IgG₁ and IgE anaphylactic antibodies and precipitins to chicken conalbumin (CA) and methylated human serum albumin (MeHSA) injected in five different regimens of immunization. These regimens consisted of various combinations of injections of antigen in water-in-oil emulsion or in saline. CA induced those antibodies well, MeHSA poorly. The mice were able to respond nearly equally at all ages, a finding differing from earlier ones for at least two reasons: (1) neither antigen used is related to any in mouse food, and (2) the regimens of immunization caused sustained antigenic stimulation together with induction of T cell responses, which could have compensated for otherwise expected age-weakening of necessary T_H cell functionings. We conclude that A/J female mice can make good anaphylactic and precipitating antibody responses to new antigens throughout life.