Publisher Summary This chapter focuses on the important discovery that virus-specific cytotoxic T cells are dually specific for virus and for a self cell surface antigen encoded by the major histocompatibility complex (MHC). The initial work was carried out on the lymphocytic choriomeningitis virus system but it soon became evident that the same phenomenon applied to many other viruses. In addition, the same principle has been found to hold for other antigenic systems, such as trinitrophenyl coupled to cells, minor histocompatibility antigens, and the H-Y model. Graft rejection and the need for genetically homogeneous inbred mouse strains for cancer research led to the development of transplantation immunology and immunogenetics. The result is that the gene complex coding for major transplantation antigens is one of the better understood mammalian genetic regions. Cytotoxic T-cell specificity is comparable to serological specificity. Because quantification of specificity or cross-reactivity is difficult, and because of the technical limitations of these cytotoxic T-cell assays, results are interpreted with great reservation. MHC restriction reflects the fact that the effector function of T cells is determined by the kind of Self-H recognized together with the foreign antigen on cell surfaces: K and D are receptors for lytic signals, I determinants are receptors for cell differentiation signals that are delivered antigen-specifically by T cells.

MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness.

Graft-versus-host disease

It has been shown that the immune response of mice to infection with L. monocytogenes gives rise to a population of immunologically committed lymphoid cells which have the capacity to confer protection and a proportionate level of delayed-type hypersensitivity upon normal recipients. The cells were most numerous in the spleen on the 6th or 7th day of infection, but persisted for at least 20 days. Further study revealed that the immune cells must be alive in order to confer protection, and free to multiply in the tissues of the recipient if they are to provide maximum resistance to a challenge infection. The antibacterial resistance conferred with immune lymphoid cells is not due to antibacterial antibody; it is mediated indirectly through the macrophages of the recipient. These become activated by a process which appears to depend upon some form of specific interaction between the immune lymphoid cells and the infecting organism. This was deduced from the finding that immune lymphoid cells from BCG-immunized donors, which were highly but nonspecifically resistant to Listeria, failed to protect normal recipients against a Listeria challenge unless the recipients were also injected with an eliciting dose of BCG. The peritoneal macrophages of animals so treated developed the morphology and microbicidal features of activated macrophages. It is inferred that acquired resistance depends upon the activation of host macrophages through a product resulting from specific interaction between sensitized lymphoid cells and the organism or or its antigenic products. Discussion is also made of the possibility that activation of macrophages could be dependent upon antigenic stimulation of macrophages sensitized by a cytophilic antibody.

https://rupress.org/jem/article-pdf/129/5/973/1083129/973.pdf

The influence of immunologically committed lymphoid cells on macrophage activity in vivo

https://www.minapharm.com/_handler/DownloadHandler.ashx?n=196.pdf&f=Attach&fileName=513.full.pdf

Leukocyte-endothelial interactions

The cellular deficit in rats thymectomized at birth is primarily one of circulating small lymphocytes. The lymphocyte deficiency is similar to that induced in adult rats by chronic drainage from a thoracic duct fistula. In both cases, the animals show a reduction of small lymphocytes in peripheral blood, thoracic duct lymph, and in circumscribed areas of lymphoid tissue. The lympocyte deficiency in lymphoid tissue can be corrected by an intravenous injection of thoracic duct lymphocytes. The evidence suggests that the deficiency is corrected by small lymphocytes. Small lymphocytes pass from blood to lymphoid tissue along a route which includes the marginal sinus in splenic white pulp and postcapillary venules in the cortex of lymph nodes and Peyer's patches. Neither the ability of small lymphocytes to colonize lymphoid tissue nor their ability to traverse postcapillary venules are thymus-dependent phenomena. However, movement of small lymphocytes across postcapillary venules appears to modify the structure of endothelium. Intravenously injected small thymocytes migrate to lymphoid tissue in smaller numbers than small lymphocytes inoculated by the same route. The few thymocytes which localize in lymphoid tissue follow the same pathway as circulating small lymphocytes.

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Migration of lymphocytes and thymocytes in the rat i. the route of migration from blood to spleen and lymph nodes

Rat bone marrow is deficient in immunologically competent cells when compared with the peripheral pool of circulating small lymphocytes. However, circulating lymphocytes capable of initiating a lethal graft vs. host reaction can develop from myeloid precursors. In adult rats inoculated at birth with parental strain bone marrow cells, the thoracic duct lymph contains cells having the immunological capability of the marrow donor. The evidence suggests that immunologically competent lymphocytes derive from cells normally resident in bone marrow and probably not from precursors in the peripheral lymphocyte pool.

https://rupress.org/jem/article-pdf/127/5/953/1082936/953.pdf

Douglas D. McGregor

Papers

Migration of lymphocytes and thymocytes in the rat i. the route of migration from blood to spleen and lymph nodes

Bone marrow origin of immunologically competent lymphocytes in the rat

Generation of macrophage chemotactic activity in situ in Listeria-immune rats.

Development of immunologically competent cells in the rat.

The mediators of acquired resistance to Listeria monocytogenes are contained within a population of cytotoxic T cells