The Thymus and the Cellular Basis of Immunity

In the humoral immune response to most antigens studied so far, the presence of helper T cells is required for the generation of antibody-forming cells from precursor B cells. In terms of the classical carrier-hapten systems described by Mitchison (1), B cells specific for a hapten can only become antibody-forming cells if helper T cells react with antigenic determinants on the carrier molecule that the hapten is linked to. This finding has later on led to the hypothesis that the close proximity brought about by an antigen "bridge" between B cell and T cell is the prerequisite for T-B cooperation (2). Under this assumption, several concepts have been developed to explain the nature of T-cell help itself. Among these are: the focussing of antigen by the T cell onto the B cell (2, 3), a membrane interaction between the two cells (4), and the production of mediators, antigen specific (5-7) or nonspecific (4,(7)(8)(9)(10)(11)(12)(13)(14), by the antigen-stimulated T cell. In vitro studies have shown that T-cell-replacing factor (TRF),I a nonantigen-specific mediator produced by activated T cells (15), can replace T cells in primary and secondary immune responses to heterologous erythrocytes (15, 16). The action of TRF and similar factors described by other authors (4, 7-14) has so far been demonstrated by restoring the immune response to heterologous erythrocytes in T-cell-deprived cultures by addition of preparations containing the factor. On the other hand, the experiments reported by Hartmann (17) have shown that T cells activated to erythrocyte antigens in vivo do, upon antigenic challenge in vitro, not only restore the response of B-cell cultures to the epitopes of the same erythrocytes, but also to those of erythrocytes from another species added simultaneously to the same cultures. Although this co-stimulation is best explained by the in situ generation and action of TRF, the function, and indeed the presence of this mediator in complete spleen cell cultures during the immune response remains to be demonstrated.In order to study this question under the most stringent conditions, we chose the anamnestic IgG reaction to soluble carrier-hapten conjugates in vitro. The pronounced T-cell dependence of the IgG response to such a conjugate and the possibility to stimulate T and B cells separately with carrier and hapten determinants make it possible to investigate the action of TRF in the immune response to soluble protein antigens.

Section: Methodssupporting

confidence: 75%

Mechanism of T-cell help in the immune response to soluble protein antigens. I. Evidence for in situ generation and action of T-cell-replacing factor during the anamnestic response to dinitrophenyl keyhole limpet hemocyanin in vitro.

Schimpl¹,

Wecker²,

Hünig³

1977

“…This conclusion has also been reached by others (1, 3, 9). On the basis of the finding that cooperation could not be brought about by humoral antibody and the impressive body of evidence demonstrating cellular cooperation between thymus-derived and bone marrow-derived lymphocytes in the induction of the immune response (6)(7)(8)(9)20), cooperation of antigenic determinants was interpreted to reflect cellular cooperation. According to this hypothesis, the induction of antibodies requires the interaction of antigen bridged helper cells and antibody forming cell precursors.…”

Section: Discussionmentioning

confidence: 99%

Determination of Antibody Class in a System of Cooperating Antigenic Determinants

Schirrmacher

Rajewsky

1970

19S and 7S memory is analyzed in a system of cooperating antigenic determinants. Cooperation occurs in the induction of both 19S and 7S secondary antibodies, and for both responses carrier specificity can be entirely accounted for by presensitization of the animal to carrier determinants. The class distribution of secondary anti-hapten antibody depends on the dose of the hapten primary-carrier conjugate used for priming, and on the time interval between priming with the hapten primary-carrier conjugate and secondary injection. The conditions of priming with the secondary carrier influence the extent of the secondary response but not the class distribution of secondary antibody. The data confirm the cooperation hypothesis of antibody induction. Specifically, we interpret them to mean that in hapten-carrier cooperation, the hapten-specific memory cells are predetermined for the class of the emerging antibodies. Together with the hapten-specific memory cells, the carrier-specific helpers are responsible for the extent of the secondary response.

“…2 Further disruption was achieved by gentle aspiration with a Pasteur pipette. The suspensions of single cells were washed three times in Eisen's solution in the case of thymus and once or twice in the case of lymph nodes or spleen.…”

Section: Methodsmentioning

confidence: 99%

Cell to Cell Interaction in the Immune Response

Miller

1970

117

Collaboration between thymus or thymus-derived lymphocytes and nonthymusderived precursors of antibody-forming ceils has been implicated in the immune response of mice to sheep erythrocytes (SRBC) I (1-3). Neonatal thymectomy impairs the response of mice to SRBC, and this can be reversed by inoculating thymus or thoracic duct lymphocytes simultaneously with SRBC (4, 5). In this system, thymus cells were as effective as thoracic duct cells and semiallogeneic cells were also effective. The identity of the antibody-forming cells produced was determined by using anti-H2 sera in allogeneically reconstituted hosts and chromosome marker analysis in a syngeneic system. These techniques demonstrated that the antibody-forming cells were, in general, derived not from the inoculated lymphocytes, but from cells already present in thymectomized hosts. Irradiated recipients of lymphoid cells from various sources were used to identify the precursors of antibody-forming cells. Thymus cells given together with SRBC failed to produce antibody-forming cells in irradiated mice, even when injected in very large numbers. A synergistic effect between thymus and marrow cells has, however, been described in such mice (6). By means of a chromosome marker method it was shown that all the antibody-forming cells produced were derived not from the thymus donor, but from the marrow donor (7). The capacity of adult thymectomized irradiated and marrow-protected mice to respond to SRBC is depressed but can be restored by the injection of thoracic duct lymphocytes (5). Semiallogeneic lymphocytes were effective in this system, and it was shown, by means of anti-H2 sera, that the antibody-forming cells produced were again derived not from