Lymphocyte transformation studies in drug hypersensitivity

In a group of patients with clinically diagnosed drug hypersensitivity the in vitro lymphocyte response to the suspected drug was assessed by the lymphocyte transformation test. The test gave positive results in all 15 patients with penicillin-induced immediate or accelerated allergic reactions and positive immediate skin-test reactivity to the major or the minor antigenic determinant of penicillin, or both, but in only 3 of the 12 patients with delayed-onset maculopapular rashes induced by penicillin, despite positive immediate reactivity to the skin-test reagents.Lymphocyte stimulation greater than five times the control level was demonstrated for five patients with penicillin-induced erythroderma, Stevens-Johnson syndrome or a serum-sickness-like illness, or with methicillin-induced interstitial nephritis, all of whom had negative reactions to the appropriate skin-test reagents. A low level of stimulation was seen in eight other skin-test-negative patients with possible allergic reactions induced by penicillins. However, in all subjects tested the stimulation was significantly greater than the mean for control subjects.For 9 of 11 patients with isoniazid-induced hepatitis or maculopapular rashes, but for only 8 of 31 patients with eruptions induced by a variety of drugs other than penicillins and isoniazid, significant stimulation occurred in the lymphocyte transformation test.It is concluded that the lymphocyte transformation test is useful in the detection of hypersensitivity to the penicillins (although in IgE-mediated reactions skin testing is clearly preferable) and isoniazid but is of limited value in the demonstration of hypersensitivity to other drugs.     

Lymphocyte transformation in casein-induced murine amyloidosis.

Spleen lymphocytes from casein-induced amyloidotic mice demonstrate diminished transformation in vitro to PHA-P, concanavalin A, and pokeweed mitogen but a normal response to lipopolysaccharide. Thymic and peripheral blood lymphocytes respond normally to these mitogens. The amyloidogen casein acted as a mitogen in both normal and casein injected mice. The diminished PHA responsiveness of spleen lymphocytes in vitro could have resulted from an inhibitory effect of amyloid fibrils on lymphocyte proliferation and did not indicate a generalized diminished cellular immunologic responsiveness of amyloidotic mice.     

Lymphocyte transformation and transmembrane potential depressors

Potassium and rubidium at high concentrations, as well as valinomycin, gramicidin, and ouabain, inhibit the PHA-induced synthesis of DNA. They act primarily at an early step in the G 1 period. All these inhibitors have in common a tendency to depress the transmembrane potential suggesting a relationship between the potential and lymphocyte transformation.     

Lymphocyte transformation induced by autologous cells.

Human peripheral blood T lymphocytes are stimulated to proliferate when cultured with autologous B-lymphoblastoid cell lines, autologous mitogen-induced lymphoblasts, or autologous non-T blood lymphocytes. This reaction, the autologous mixed lymphocyte reaction, has attributes of an immune response possessing both memory and specificity. The capacity to stimulate autologous T lymphocyte proliferation depends on the lineage of the lymphoid cell and not on its establishment in continuous culture or carriage of the EB viral genome. The determinant on non-T lymphocytes which stimulates the autologous mixed lymphocyte reaction appears to be an Ia determinant. Thus, allogeneic graft rejection and the allogenic mixed lymphocyte reaction are very likely extensions of an immune response expressed within the host.     

Lymphocyte transformation test--basis and clinical use]

The principle of the lymphocyte transformation test is represented and the present knowledge of the partially selective effect of various unspecific mitogenes on different lymphocyte populations is referred to. Problems of methodology are briefly dealt with and the possibilities of applying the lymphocyte transformation test is referred to in detail. Own experiences are reported on the basis of clinical examples in patients affected with malign lymphoma, infectious mononucleosis and polymyositis.     

The antifibrinolytic activity of sulfamylon solution

Sulfamylon (mafenide) solution, a potent experimental topical antimicrobial, is used in our burn unit to treat burn wounds both before and after skin grafting. The importance of fibrin to early graft adherence prompted this in vitro study of the effect of Sulfamylon upon fibrin clot. Assessing fibrinolysis by in vitro proteolysis of [125I] fibrin monomers, Sulfamylon, at relevant clinical concentrations, produced dose-related inhibition of streptokinase-mediated fibrinolysis. In addition, Sulfamylon had no intrinsic fibrinolytic activity. This antifibrinolytic property of Sulfamylon solution may, in vivo, protect against early graft loss when used on burn wounds and other potentially contaminated graft sites.