We have previously demonstrated that lymph nodes draining the site of an allograft reaction selectively retain long-lived lymphoid cells, in part on the basis of the immunological specificity of the cells involved (1). The relatively small immunologically specific component in this accumulation was demonstrated by a double isotope dilution method, in which cells sensitized to one set of histocompatibility antigens were labeled in vivo with thymidine-3H and cells sensitized to a different set of histocompatibility antigens were labeled with thymidine-~4C, under conditions where most of the label was confined to the long-lived cells (1-3). The ceils were then pooled and adoptively transferred to syngeneic hosts who were then challenged with both sets of antigens. Immunological specificity was inferred from the small but consistent excess of cells from the donors immunized to each set of antigens in the lymph nodes stimulated by that same antigen 6-8 days after challenge grafting. In these initial studies (1) we deliberately selected an immunological reaction that was principally dependent on cell-mediated immunity (an allograft reaction in H-2-compatible strains). The present studies were designed to ascertain whether a similar selective accumulation of long-lived lymphocytes occurs in lymph nodes stimulated by antigens evoking principally an immunoglobulin-mediated response, and to demonstrate a similar immunologically specific component in this accumulation.
One of the basic effects of antigens on lymphocytes is to stimulate DNA synthesis and cell division. This effect is readily demonstrable in vitro (1-3) and in vivo (4-7). Thymus "independent" antigens may stimulate DNA synthesis by B lymphocytes only (8, 9) or by both T and B lymphocytes (10, 11), while thymus-dependent antigens typically stimulate DNA synthesis by both T and B cells (12, 13), with the response of the T ceils generally preceding that of the B cells (5, 13). While some of this accelerated DNA synthesis reflects the activity of specific clones of lymphocytes with surface receptors for the antigen selected (14-17), much of it also seems to reflect the activity of cells with no intrinsic specificity for the antigen (15,16,(18)(19)(20)(21)(22)(23)(24)(25). These latter cells presumably are responding to mitogenic factor (18, 19), possibly to other T cell products (20-25) and possibly to other substances whose sources are not presently defined. This background of nonspecific stimulation has made it very difficult to study the antigen-induced DNA synthesis of specifically reacting cells directly.We have recently described a system whereby it is possible to concentrate recirculating long-lived lymphocytes of a particular specificity by secondary antigenic stimulation (15,16). Unfortunately this secondary stimulation also results in the nonspecific trapping of many other long-lived recirculating lymphocytes in the same lymph nodes (15, 16). The present studies, which were undertaken to try to refine this system, are based on the following two observations: first, most rapidly dividing lymphoid cells do not ordinarily recirculate (26) and therefore have little tendency to accumulate in antigenically stimulated lymph nodes (27, Emeson, Thursh, and Noble, unpublished observation), and, second, cells with specific reactivity for an antigen seem to rapidly synthesize DNA at very specific times after antigenic stimulation (28, 29). It was hoped that labeling cells for a very brief period after antigenic stimulation might make it possible to define conditions where specifically reactive cells were labeling much more rapidly than other recirculating
Graft-vs.-host (GVH)-induced lymphadenopathy of the popliteal lymph node has been produced in C57BL/6 x A/J F1 (BAF1) mice by injecting A/J spleen cells into the rear footpads. By giving 51Cr-labeled BAF1 lymphoid cells intravenously to the hosts, 24 h before sacrifice, we have demonstrated that a large portion of the GVH-induced lymphadenopathy is due to the trapping of circuating lymphocytes in the challenged lymph nodes. Most of the remaining enlargement can be attributed to proliferation of host cells within the reacting lymph nodes. Conditions have been defined under which the weights and [14C]thymidine incorporation of the popliteal nodes can be plotted against the dose of injected A/J spleen cells on a double-log scale to give a linear dose-response. The popliteal lymph node GVH assay is a simple and effective means of quantitating immune reactivity to histocompatibility antigens in mice.
A knowledge-based Hypertext of Pathology integrating videodisc-based images and computer-generated graphics with the textual cognitive information of an undergraduate pathology curriculum has been developed. The system described in this paper was implemented under HyperCard during 1988 and 1989. Three earlier versions of the system that were developed on different platforms are contrasted with the present system. Strengths, weaknesses, and future extensions of the system are enumerated. The conceptual basis and organizational principles of the knowledge base are also briefly discussed.
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