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Enhancement and inhibition of immunological mechanisms by immunosuppressive agents. I. Dose effect on priming and generation of memory to a bacterial antigen.

A new experimental system is described which allows the study of the effect of immunosuppressors upon the priming and generation of memory to an antigen from Escherichia coli. A single dose of bacterial beta-D-galactosidase without adjuvant injected into C57B1/6J mice primes and elicits memory but not antibodies. Thus by administering immunosuppressors near the priming injection, one can examine whether primary antibody formation is enhanced and whether priming generation of memory is enhanced or inhibited. We found that X-rays, cyclophosphamide and oxisuran (2-[(methylsulfinyl)acetyl]pyridine) either enhance or inhibit the elicitation of memory, depending on dosage, although they do not alter primary antibody unresponsiveness. The data show two main features: (a) immunosuppressors can enhance immunization; and (b) generation of memory can be improved without increasing antibody levels. The former finding draws attention to the role that immunosuppressors might play in the breaching of tolerance to self-antigens which share determinants with microbes, while the latter observation shows that antibody synthesis and elicitation of memory can follow independent pathways.