▪ Abstract Meiotic chromosomes have been studied for many years, in part because of the fundamental life processes they represent, but also because meiosis involves the formation of homolog pairs, ...

Meiotic chromosomes: integrating structure and function.

Publisher Summary The term “cell-mediated cytotoxicity” applies to lytic reactions that require the participation of lymphoid or non-lymphoid cells but not of added complement. It has been clearly established that several pathways, including different cell types, are involved in cytotoxic reactions in vitro. With membrane-associated antigens, such as transplantation, and tumor-associated antigens, the cytotoxic effect of effector cells on adequate target cells is most often highly specific and requires intimate contact rather than release of diffusible toxic factors. Specific cell-mediated cytotoxicity in vitro can be divided into three categories according to the nature of the effector cells.

Cell-Mediated Cytotoxicity, Allograft Rejection, and Tumor Immunity

Publisher Summary This chapter attempts to identify the principles and issues elucidated in animal models that may provide insights for the development of effective approaches to modulate T cell functions to promote the eradication of human tumors. The importance of T cells in surveillance against the outgrowth of tumor cells is probably best demonstrated with virally transformed tumors, such as EBV-induced B cell lymphomas, which occur with markedly increased frequency in transplant patients specifically depleted of T cells, and with UV-induced squamous cell cancers that occur with high frequency in renal transplant patients. Second, the reasons for the growth of presumably immunogenic tumors in immunocompetent hosts have become more apparent with an improved understanding of the function of T cell subsets and the requirements for the induction and expression of T cell responses. The earlier perceptions that cytotoxic T cells recognize foreign proteins integrally inserted in the cell membrane had focused efforts for more than a decade on the use of the powerful new monoclonal antibody technology combined with biochemical purification techniques to isolate tumor antigens expressed on the cell membrane. However, analyses of the requirements for recognition of virally infected cells by CD8 + cytotoxic T cells demonstrated that Class I-restricted T c do not recognize integral membrane proteins but rather recognize intracellular proteins that are synthesized in the cytoplasm. Tumors containing unique or mutated and potentially immunogenic cellular proteins may selectively or predominantly elicit only CD4 + or CD8 + T cell responses because the antigen is adequately presented in the context of only one MHC molecule, and in this setting only T cells from the subset restricted to that MHC molecule appear effective in tumor therapy.

Adoptive T cell therapy of tumors: mechanisms operative in the recognition and elimination of tumor cells.

Publisher Summary This chapter reviews the evidence for cell-mediated immune reactions against tumors in animals and man, particularly, the reactions that can lead to destruction of neoplastic cells cultivated in vitro. Various mechanisms by which tumor cells can escape from immunological destruction have been discussed, most notably one involving blocking factors, present in the serum. Findings analogous to those obtained when studying tumor immunity (coexistence of cell-mediated reactivity and blocking serum activity) have been summarized from three other areas (pregnancy, allografting, and chimeras). The studies reviewed in the chapter have given a relatively large amount of evidence for various cell-mediated and humoral immunological reactions against growing tumors, and at least some of the reactions observed in vitro appear to be able to influence tumor growth in vivo .

Lymphocyte-Mediated Cytotoxicity And Blocking Serum Activity To Tumor Antigens

Cancer metastasis. Organ colonization and the cell-surface properties of malignant cells.

THE increase in anti-microbial activity of macrophages which occurs in animals that have been infected with living microorganisms is frequently non-specific1. In contrast, the anti-tumour activity of macrophages from immunized animals has been demonstrated in vitro to be immunologically specific2,3. The experiments to be described may throw light on this paradox. They show that the killing of tumour cells by macrophages is made up of an immunologically specific interaction which is followed by a non-specific lethal reaction. A similar pattern has been described for the bactericidal action of immune macrophages3. We have described three ways of obtaining immunologically specific macrophages cytotoxic to tumour cells3,5. These are (1) from the peritoneal cavity of suitably immunized mice (see later); (2) “arming” in vitro by contact of non-immune macrophages with spleen cells from hyperimmunized mice, and (3) “arming” in vitro by exposure of non-immune macrophages to the cell-free supernatant obtained when spleen cells from immunized mice are cultured with the specific antigen. All such macrophages, on coming into contact with specific antigens, undergo a transformation (referred to as “activation”) which renders them capable of killing. The actual destruction of the target cell following direct contact with the “activated” macrophages is non-specific. Moreover, this non-specific killing may also be demonstrated by macrophages “armed” against tubercle bacilli (BCG) which are “activated” after exposure to the solubilized protein derivative from tubercli bacilli, PPD, and are able to kill tumour cells. In the original experiments3,5 in which target lymphoma cells were added to “armed” macrophages the immunologically specific stage and the non-specific stage of the cytotoxic reactions were not separated and occurred sequentially (Fig. 1).

R. Evans

Papers

Mechanism of Immunologically Specific Killing of Tumour Cells by Macrophages