Radiation-induced augmentation of the immune response has been shown to occur both in vivo and in vitro. Evidence is presented to implicate injury to an extremely radiosensitive T cell in the expression of this phenomenon. Experiments are outlined which could be employed to support or reflect this hypothesis.
In this chapter I have dealt with the cellular and genetic basis of regulation of the immune response to tumor antigen. I have knowingly omitted discussion of effectors such as ADCC, NK, and B cells, since my own experience with such effectors relates primarily to early events associated with small-tumor inocula (Greenberg and Greene, 1976). In that model, NK and ADCC mechanisms, in which natural antibody and macrophages participate, are of importance and T cells are not. In the studies I have dealt with herein, more advanced tumor models have been evaluated. It is clear, I hope, from this chapter that understanding the pathways to immune-cell or Ts activation will provide the basis for applied immunotherapy techniques in the future.
T cells are responsible for virtually all the characteristics of the mammalian immune system except the production of serum antibody, in which they play a vital regulatory role. As such, they are central to our understanding of the immune system. T cells recognize cell-bound antigens with great precision, in association with self MHC antigens. They do this by means of antigen-specific receptors, whose antigen-combining sites are encoded in conventional VH genes. There is evidence that T cells carry at least two kinds of specific receptors, one for MHC antigens and one for non-MHC antigens. Both of these would bear VH-encoded and distinct idiotypic determinants. The process by which antigens associate with MHC-gene products on cell surfaces is poorly understood at present, and so is the process by which the two types of receptors communicate with each other. T cells are divisible into a number of subpopulations playing unique functional roles in the regulation of antibody responses. If one examines them further for other functions, even greater complexity emerges. Thus, all T cells may not have the same kind of receptor, which would not be surprising given the wide variety of functions they perform. Future work will undoubtedly focus on these important questions.
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