Cell to Cell Interaction in the Immune Response

Abstract

An injection of viable thymus or thoracic duct lymphocytes was absolutely essential to enable a normal or near-normal 19S liemolysin-forming cell response in the spleens of neonatally thymectomized mice challenged with sheep erythrocytes. Syngeneic thymus lymphocytes were as effective as thoracic duct lymphocytes in this system and allogeneic or semiallogeneic cells could also reconstitute their hosts. No significant elevation of the response was achieved by giving either bone marrow cells, irradiated thymus or thoracic duct cells, thymus extracts or yeast. Spleen cells from reconstituted mice were exposed to anti-H2 sera directed against either the donor of the thymus or thoracic duct cells, or against the neonatally thymectomized host. Only isoantisera directed against the host could significantly reduce the number of hemolysin-forming cells present in the spleen cell suspensions. It is concluded that these antibody-forming cells are derived, not from the inoculated thymus or thoracic duct lymphocytes, but from the host. Thoracic duct cells from donors specifically immunologically tolerant of sheep erythrocytes had a markedly reduced restorative capacity in neonatally thymectomized recipients challenged with sheep erythrocytes. These results have suggested that there are cell types, in thymus or thoracic duct lymph, with capacities to react specifically with antigen and to induce the differentiation, to antibody-forming cells, of hemolysin-forming cell precursors derived from a separate cell line present in the neonatally thymectomized hosts.

The Role of Nonlymphoid Accessory Cells in the Immune Response to Different Antigens

“…A related aspect is the possible interaction between different lymphoid cells. Evidence for such an interaction in the response to SRC has been provided by in vivo studies (e.g., 19,28) and to some extent from in vitro work (23,30). Again this aspect will be investigated using the density separation technique, but care will be needed to experimentally separate lymphocyte-lymphocyte interaction from the lymphocyte-accessory cell interaction considered in the present report.…”

“…However, it remained entirely possible that the actual progenitors of the hemolytic antibody-forming cells were contributed by the lymphocytes in the adherent fraction (or the irradiated host for the in vivo assay), lymphoid cells in the filtrate fraction serving some essential accessory role such as antigen recognition. Such an interaction between different classes of lymphocytes has been described for the SRC response (19,28). To test this possibility, the adherent fraction from C57 mice was mixed with the filtrate fraction from CBA mice, and the origin of antibody-forming cells resulting from stimulation in culture with SRC was tested with the aid of strain-specific anti-H2 isoantisera.…”

Translating Molecular Insights in Autoimmunity into Effective Therapy

“…With Graeme Mitchell, he had just published a series of three landmark papers (9)(10)(11) documenting that thymus-derived lymphocytes did not in themselves make antibody or develop into antibodyforming cells, but rather interacted with and activated bone marrow-derived antibodyforming cell precursors. He had also recently been elected a fellow of the Royal Society, ahead of the other two scientific giants at WEHI, Gus Nossal and Don Metcalf.…”

“…Tony provided a series of irradiated mice repopulated with thymus cells only, a source of relatively pure T cells (9), and I put them in culture with a variety of other populations, usually adult thymectomized bone marrowgrafted mice (14) that Tony had also provided, where B (but not T) lymphocyte repopulation takes place. To study the process in more detail, I developed a variant of the MarbrookDiener culture system that I had been using to study a variety of immunological processes in vitro, including immunological tolerance.…”

Maturation of Hemolysin-Producing Cell Clones

“…At least a two cell interaction is required in the transfer system first described by Claman et al (16). Using this system (23)(24)(25), it has been postulated that antigen must somehow interact with a thymus derived cell, termed the antigen-reactive cell (ARC) before successful stimulation and maturation of the bone marrow derived immediate antibody-forming cell precursor (AFCP = PPFC) could take place. For this type of interaction to be true for the observation of the simultaneous stimulation of PPFC resulting in synchronous division reported here, certain conditions would have to exist.…”