On the Number and Nature of Antigen-Sensitive Lymphocytes in the Blood of Delayed-Hypersensitive Human Donors

Abstract

Considerable progress in our understanding of the basic mechanisms of delayedtype hypersensitivity has been made in recent years, largely as a consequence of studies in vitro (1, 2). Although most of these studies have approached the problem primarily at the phenomenological level, they have established that the immunological information necessary for the initiation of cell-mediated immune reactions in vitro is possessed by the small lymphocyte which, upon interaction with specific antigens can influence, directly or indirectly, a variety of other cells in its environment.In order to study the cell-mediated immune response on a quantitative basis, we have recently developed a plaque assay which permits determination of the number of antigen-sensitive cells within a population of lymphoid cells (3). The method was designed to detect intrinsic changes produced in sensitized lymphocytes as a consequence of activation by antigen, rather than to measure products secreted by such cells. The basis for our approach is that unstirnulated lymphocytes generally do not support replication of viruses, whereas antigen-activated lymphocytes do so.The quantitative approach to delayed-hypersensitivity reactions in man is of interest at two levels. Because of their importance in the rejection of allografts and tumors, and in the course of some "autoimmune" diseases, there is an urgent need for quantitative measurements in vitro of cell-mediated immunity at the clinical level. We can hardly imagine a clinically useful analysis of an immune response mediated by antibodies if it could be demonstrated only by means of the wheal-and-flare reaction. Yet skin tests are still the principal measure of delayed hypersensitivity in man. Secondly, a method that permits enumeration of specifically sensitized cells is of obvious value for approaching an understanding of the basic mechanisms underlying the delayed-* Recipient of U. S.

Cell-Mediated Cytotoxicity During Rejection and Enhancement of Allogeneic Skin Grafts in Rats

“…In the latter animals CL were calculated to be 0.5 % in lymph nodes and 0.3 % in spleens and peripheral blood. The calculated number tallies well with the calculated number of effector cells in lymphoid tissues of guinea pigs (37) and in peripheral blood of humans (38) with delayed hypersensitivity. Henney determined a similar small number per II-2 antigen in sensitized mice (18), as did Brunner (39) (36) by measuring uptake of thymidine-3H.…”

Cellular and Humoral Effects of Hyposensitization in Patients with Summer Hay Fever

“…The immuni zation procedure would, in the first instance, induce proliferation of the antigen responsive lymphocytes and eventually result in the production of an effector cell, which could be a non-dividing, MIF producing T-lymphocyte which comes nevertheless from a dividing cell precursor. The vi rus plaque assay of Jimenez et al [5] would be an illustration of this.…”

Generation of cytotoxic T lymphocytes in vitro. IV. Functional activation of memory cells in the absence of DNA synthesis.

“…Hayry and Andersson (12) also found that the formation of large lymphoid cells after restimulation of long-term MLC cells with the relevant alloantigens was unaffected by the presence of hydroxyurea, an inhibitor of DNA synthesis, but no data on CTL function under such conditions were reported . Using a virus plaque assay, Jimenez et al (13) observed that the antigen-dependent activation of presumably immune T cells was unaffected by the presence of a mitotic inhibitor . More recently, the differentiation of mitogen-stimulated B lymphocytes into functional antibody-producing cells in the absence of DNA synthesis has been demonstrated by Andersson and Melchers (14) .…”