Shmuel Livnat

The cell-mediated immune response: interactions of initiator and recruited T lymphocytes.

The cell-mediated immune reaction, for heuristic purposes, has been divided into three phases analogous to the spinal motor nerve reflex arc. The sensitization or afferent phase may be triggered outside the lymphoid organs by contact between lymphocytes and immunogen (Medawar 1958, Turk 1967). The second, or central, phase of the reaction takes place in the draining lymph node (Mitchison 1955, Stark et al. 1960, Billingham et al. 1963). The lymph node swells with an increased number of cells as lymphocytes differentiate into effector, memory and possibly suppressor cell types. In the third, or efferent phase, effector lymphocytes emigrate from the central lymph node and mediate the immune response (Billingham et al. 1954, Hall 1967, Pederson & Morris 1970). Memory of the immune stimulus is stored in the system and can be demonstrated as an accelerated secondary response upon rechallenge with the speciflc immunogen (Billingham et al. 1954, Mitchison 1955, Gowans & Uhr 1966). It has been feasible to isolate and analyze the first and last components of the immune reflex so that much important information has been gathered regarding immunogens which trigger the reaction (Sela 1969, Schlossman. 1972) and the effector lymphocytes that are subsequently generated {Transplantation Reviews 17, 1973). However, the events which comprise the intermediate stages of the immune response have been less amenable to study. What is the relationship between the afferent lymphocytes which initially are triggered by immunogen and the efferent lymphocytes which

Interactions of Initiator and Recruited T Lymphocytes in Cell-Mediated Immunity

Publisher Summary This chapter discusses the characterization of the cells and illustrates the signals, which comprise the flow of immune information, leading to the generation of T-cell-mediated immunity. A T-cell-mediated response requires the sequential interaction of at least two distinct types of T lymphocytes. One type of lymphocytes, initiator T lymphocytes (ITL), are the agents of the afferent sensitization phase of the reaction. The development of effector and memory lymphocytes requires the recruitment by the ITL of another type of T lymphocyte in the central lymph node phase of the response. The recruited T lymphocytes (RTL) appear to be a part of a circulating pool of lymphocytes that includes those that mediate a graft-versus-host (GVH) reaction. Hence, RTL are trapped and activated by the double signal of syngeneic ITL plus immunogen. Systemic memory of the primary response is found to be associated with the appearance of new ITL. Those findings represent an approach towards integration of diverse immune phenomena such as the transplantation and GVH reactions.

Recruitment of effector lymphocytes by initiator lymphocytes: recruited lymphocytes are immunospecific.

We have been investigating T lymphocyte interactions in the development of effector lymphocytes in a cell-mediated immune response (1–3). We found that mouse or rat initiator lymphocytes, sensitized in vitro against allogeneic fibroblasts, recruit syngeneic effector T lymphocytes. This recruitment reaction can be triggered in the draining popliteal lymph nodes (PLN) of animals by injecting their hind footpads with in vitro sensitized initiator T lymphocytes. The initiator lymphocytes do not themselves proliferate or differentiate into effector cells. Instead, T lymphocytes of the recipient accumulate in the enlarging PLN. These recruited T lymphocytes were found to mediate immunospecific cytotoxicity in vitro, or allograft rejection in vivo, against the same antigens which induced sensitization of the initiator lymphocytes.