Geoffrey H. Sunshine

Antigen-presenting cells do not discriminate between self and nonself.

The immune response to F protein in mice provides a system in which the capacity of antigen-presenting cells to present autologous protein to T cells can be examined. When we used the F-type 1 (F.1) and F-type 2 (F.2) combination, these cells proved equally able to present autologous and foreign protein in both an in vivo adoptive transfer and an in vitro proliferation assay. This formally excludes the possibility that these cells themselves discriminate between self and nonself, while still allowing the possibility that their uptake of antigen may be regulated by lymphocyte products.

A comparative study of accessory cells derived from the peritoneum and from solid tissues.

Accessory nonlymphoid cells are an essential component of the in vitro immune response and are a major site of genetic restriction in these responses. However, the identification of in vivo accessory cell analogues in solid lymphoid tissue is difficult. The separation and purification steps are complex. Even when cells are obtained these may have lost the distinguishing features which permitted their recognition in tissue section.

Antigen Presentation by Dendritic Cells

Until quite recently, the dogma on immune activation could be summarized as follows: antigens were engulfed and devoured (processed) by a specialized cell, the macrophage, characteristically adherent, phagocytic and radioresistant. A degraded fragment of the consumed antigen then reappeared on the surface of the ingesting cell and was then recognized by a T lymphocyte in association with MHC subregion antigens (H-21 in the mouse) on this same “fresser” cell (presentation) (1). Whilst it is clear that macrophages can certainly ingest and degrade antigens of all shapes and sizes, there is little if any direct evidence that the events defined by the term “presentation” are the responsibility of the same cell. Thus, there is as yet no convincing evidence that antigen fragments are actually re-expressed on the macrophage cell surface let alone that they are presented or associated with macrophage H-21 antigens.

RES-Leukocyte Interactions

The physiology of RES-leukocyte interactions is a difficult topic to discuss in a single chapter, as this brief title encompasses an incredible diversity of cells which influence each other in a bidirectional manner. Our first premise in this discussion is that RES cells and leukocytes are the basic constituents of the immune system, and that this should be the chief focus of our attention.

Role of the Reticuloendothelial System in T-Helper Cell Induction

The development of in vitro culture systems and cell separation methods has provoked increasing interest in understanding the role of RES accessory cells (AC) in immune induction. As the relevant technology was improved, AC were found to be important in every immune function assayed, such as antibody production in vitro (Mosier, 1969), killer cell induction (Wagner et al., 1972), mixed leukocyte reaction (MLR) (Greineder and Rosenthal, 1975), T-cell proliferation (Rosenwasser and Rosenthal, 1978), etc. Apparent exceptions early on (Diener et al., 1970) were almost certainly reflections of the different types and numbers of AC required for various responses, and also of the inefficiency of AC depletion by conventional adherence procedures which are usually only maintained for the depletion of classical macrophages. Accordingly we were not surprised that T-cell help in vitro required macrophages (Erb and Feldmann, 1975a) .

Monoclonal Antibodies Against Ia +, Antigen Specific T Cell Factors

Abstract We have produced a xenogeneic (rat) monoclonal antibody (AF3.44.4) against mouse T cell helper factors (HFs). This antibody will bind HFs of various strain and antigen specificities and therefore appears to recognise a ‘constant’ region. We report here the effects of this monoclonal antibody on in vitro immune responses.

Antigen Specific Helper Factors: An Overview after Ten Years

Immunology in the late 1960’s was a time of rapidly changing concepts. The functional dichotomy of T cells and B cells had been enunciated (reviewed Roitt et al., 1969, Greaves et al., 1972), the puzzle of Immune Response genes had been uncovered (Kantor et al., 1963) and receptor antibodies had been visualized on B cells but not T cells (Taylor et al., 1971). The carrier effect had been described and the phenomenon of linked recognition had suggested various molecular models (Mitchison et al., 1970) to account for the mechanism of T cell cooperation (or help). These models, represented in Fig.1, involved a ‘carrier antibody’ derived from the T cell recognizing carrier determinants on the antigen, whose ‘aptenic’ determinants interacted with B cell receptors. This could either occur with direct T-B contact, or indirectly with the ‘carrier antibody’ being released from the T cell. No formal test of the direct contact hypothesis was possible in 1971, and no direct test has yet been performed. However, a test to determine whether effective help could occur without T-B contact was feasible in tissue culture, by separating T cells and B cells by a cell impermeable membrane, which nevertheless permitted macromolecules to pass through.

Ia and Macrophages in Alloproliferation and Allocytotoxicity

Current experiments on primary allogeneic responses in our laboratory are based on the observation that the prototype macrophage washed out of the peritoneal cavity does not stimulate allogeneic T cell proliferation in vitro (1) but does stimulate T helper cell induction (2) and cloned antigen specific T helper cells (3). The dendritic cell which clearly differs from a conventional macrophage is exceptional in its efficiency in primary mixed lymphocyte culture (MLC) stimulation (1). Another contrast of major immunologic relevance between these two cell types is that peritoneal macrophages do not express Ia (or Class II MHC products) on their surface to any great extent (usual range 5–10% specific fluorescence) whereas dendritic cells are strongly Ia positive (70–80%).