Loss of tumor-specific and idiotype-specific immunity with age.

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Abstract
The UV light-induced [mouse] fibrosarcoma 1591 undergoes first-set rejection when transplanted into normal syngeneic mice. The primary resistance of normal mice decreases wigh age, beginning at 9-12 mo. equivalent to middle age for mice. Mice lose with age the capacity to mount idiotypic and anti-idiotypic responses responsible for controlling the tumor growth. This loss was correlated with quantitative as well as qualitative changes in the response, such as changes in specificity and clonotype. Normal young mice regularly expressed a dominant common anti-1591 idiotype as defined by an anti-idiotypic probe. The capability of normal mice to respond with lymphocytes of this dominant common idiotype began to decline at about 8 mo. of age. At this time, animals still generated tumor-specific lymphocytes, but these lymphocytes appear to be idiotypically different lymphocyte clones. With further increase in age, animals responded with tumor-reactive lymphocytes that showed a marked cross-reactivity to other tumor target cell lines. Both in vivo and in vitro, the capability of normal mice to mount an immune response that was specific for the 1591 tumor cells decreased between 9 and 14 mo. which was the age individual mice became increasingly susceptible to a challenge with 1591 tumor cells. Clones of tumor-specific T cells apparently provide primary and early protection of young animals against challenge with malignant 1591 cells. The dominance of these tumor-specific T cell clones in a primary immune response is lost in middle-age. Because of the ability of animals to mount anti-idiotypic immune responses also declined in middle-aged animals, it is possible that the observed loss of clonal dominance of tumor-specific clones with increasing age is at least partially related to age-dependent changes in the anti-idiotypic compartment.

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