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T B Strom

Publications and source records attributed to T B Strom.

At least 289 records · Page 16Linked to original sources
PubMed1982

Evidence for the presence of suppressor T lymphocytes in animals treated with cyclosporin A.

Mice sensitized with alloantigens and treated with cyclosporin A (CsA) were incapable of generating antigen-specific cytolytic lymphocytes (CL). Lymphocytes from these CsA-treated animals could not be reactivated upon exposure to the same alloantigens in mixed lymphocyte culture (MLC), whereas their response to a third-party antigen remained intact, suggesting a long-lasting and specific effect of CsA. After being irradiated, these lymphocytes from CsA-treated animals were added to normal MLC and were shown to prevent normal lymphocytes from becoming cytolytic in a dose-dependent and antigen-nonspecific fashion. These suppressor cells were not detected in mice receiving CsA only, indicating that CsA did not induce but rather permitted the expression of suppressor cells possibly generated by allosensitization. The suppressor cells appeared to be T lymphocytes, because treatment with anti-Thy-1.2 antibody and C abrogated their suppressive activity. The present results suggest that activation and/or sparing of suppressor cells by CsA may account for the long-lasting unresponsiveness seen in CsA-treated animals.

Animals↗
PubMed1982

Human serum-free mixed lymphocytes response: the stereospecific effect of insulin and its potentiation by transferrin.

We have established a serum-free human mixed lymphocyte response (MLR). Proliferative unidirectional responses are discerned using peripheral blood leukocytes obtained from unrelated individuals and family members mismatched for HLA while MLR conducted between HLA identical siblings are negative. Resting lymphocytes lack insulin and transferrin receptors; activated lymphocytes are known to express insulin and transferrin receptors. Interestingly, physiologic concentrations of insulin and transferrin synergistically potentiate DNA synthesis in serum-free allogeneic cultures. To verify that the insulin effect was due to a stereospecific interaction between insulin and classical, high-affinity insulin receptors, insulin and a series of insulin-like peptides were compared in their ability to bind to alloactivated T cells and amplify the MLR. The results demonstrate the stereospecificity of the insulin effect in the MLR and underscore the importance of lymphocytic insulin receptors in the process of lymphocyte activation.

Animals↗
PubMed1982

Expression of T cell differentiation antigens and Ia on rat cytotoxic T lymphocytes.

Study of lymphocyte subsets has been facilitated by the detection of various surface markers that are related to distinct functions. We have explored the use of affinity methods for separation of large quantities (10(8)) of rat cells and used this technique to identify surface markers of cytotoxic T lymphocytes. Splenocytes from animals bearing skin allografts for 7 days were depleted of B cells and were separated into T cell subsets by using W3/25 and OX8 monoclonal antibodies, which mark two nonoverlapping populations of peripheral T cells. Our results demonstrate that the cytotoxic T cells are W3/25- and OX8+. They also bear minimal or no Ag-F alloantigen, a peripheral T cell marker, and they express Ia-like products analogous to those of the mouse I-A subregion but not of the I-E/C subregion.

Animals↗
PubMed1982

Restoration of allograft responsiveness in B rats by interleukin 2 and/or adherent cells.

LEW X BN)F1 cardiac allografts survive 1 wk in unmodified LEW recipients (MST +/- SD = 8.3 +/- 1.2 days) but indefinitely (greater than 100 days) in B rats, produced by 750 R sublethal x-radiation 3 to 4 wk after adult thymectomy and reconstitution with syngeneic bone marrow cells from thymectomized thoracic duct-drained donors. Graft survival appears independent of blocking antibodies and is not mediated by suppressor cells or loss of graft immunogenicity. The unresponsive state is eventually reversed by adoptive transfer of 10(8) spleen cells from nonimmune (MST +/- SD = 27.5 +/- 4.7 days) or alloimmune (MST +/- SD = 21.5 +/- 1.9 days) syngeneic animals. In contrast, concomitant administration of 2 X 10(7) thioglycollate-stimulated peritoneal exudate adherent cells plus 10(8) alloimmune syngeneic spleen cells produced acute allograft rejection in 50% of B recipients within 10 to 12 days, while in every instance grafts underwent acute rejection (MST +/- SD = 10.0 +/- 1.4 days) in B recipients treated with interleukin 2 (IL 2) rich conditioned supernatant plus sensitized cells. In vitro studies revealed that adherent cells from B rats possessed less than 50% the capacity of adherent cells from normal animals either to support the Con A-stimulated uptake of 3H-thymidine by splenic T cells or to promote production of IL 2 by spleen cells depleted of adherent cells. Altered lymphocyte migration patterns in B recipients may also contribute to prolonged allograft survival secondary to adherent cell dysfunction.

Animals↗
PubMed1981

Clinical and experimental aspects of renal allograft rejection.

The pathophysiology, differential diagnosis, and clinical management of renal allograft rejection is reviewed. Recent data have revealed the discriminant biochemical and functional attributes of Class I (HLA-A,B, and C) and Class II (HLA-DR) major transplantation antigens. Graft rejection is an intricate process in which several cytodestructive mechanisms may coexist. The role of donor-specific and nonspecific immunologic monitoring tests in patient management is reviewed. Acute cellular rejection is usually readily reversed by high dose corticosteroid therapy while chronic humoral rejection is refractory to such treatment. Treatment of steroid-resistant rejection episodes by plasmapheresis/antilymphocyte globulin is under investigation.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1981

Cyclosporin A spares selectively lymphocytes with donor-specific suppressor characteristics.

The effect of cyclosporin A (Cy A) on the host responses to heart allografts have been examined in rats following administration of the drug for 7 days after grafting. All grafts functioned greater than 100 days without rejection episodes in animals of major histocompatibility differences. Thymic or splenic lymphocytes (1 X 10(8) from LEW recipients of (LEW X BN)F1 hearts were transferred at varying periods into untreated LEW rats transplanted with (LEW X BN)F1 test hearts 24 hr later. Test grafts survived 12 to 16 days significantly (P less than 0.001) longer than in untreated animals (MST +/- SD = 7 +/- 0.3 days). Cells from normal LEW animals, Cy A-treated but ungrafted, and grafted but not treated animals, all failed to prolong test graft survival. Specificity of the effect was tested in vivo, using hearts from donor and third-party rats, and in vitro, using the mixed lymphocyte response (MLR). In vivo, thymocytes from treated LEW recipients of (LEW X WF)F1 grafts failed to prolong (LEW X BN)F1 test grafts; conversely, transferred thymocytes from LEW recipients of LEW X BN)F1 grafts failed to prolong (LEW X WF)F1 grafts. The MLR of lymphocytes from Cy A-treated rats was significantly decreased against donor lymphocytes but not against third-party lymphocytes. Additionally, both cellular and humoral immunity mounted by Cy A-treated recipients was depressed throughout the entire follow-up period. Prolonged heart graft survival after 7 days of Cy A treatment suggests emergence of cells with specific suppressor activity, which in turn may cause profound abrogation of host effector responses against vascularized organ allografts.

Animals↗
PubMed1981

A patient with post-hepatitis B immune deficiency: nonspecific helper factor partially restores the in vitro immune response.

A patient with severe post-hepatitis B aplastic anemia had depressed B and T cell responses. In mixed leukocyte culture, her cell were unresponsive to unrelated control stimulating cells, but responded well to a pool of cells from the same unrelated controls. She had reduced production of lymphocyte mitogenic factor (MF), suggesting a helper cell defect, and she had few or no cells reactive with the monoclonal anti-T cell antibodies OKT3, OKT4 or OKT5. Her cells proliferated in response to MF produced by a pool of cells without mitogen, however. Furthermore, her cells became specifically cytotoxic when stimulated by cells plus MF, but not when stimulated by either cells or MF alone. Thus her T cell deficiency was correctable by nonspecific helper factor in vitro.

Adolescent↗
PubMed1981

Rapid mixed lymphocyte culture testing by analysis of the insulin receptor on alloactivated T lymphocytes: implications for human tissue typing.

Responses in the mixed lymphocyte culture (MLC) are traditionally evaluated by measurement of DNA synthesis or blast transformation. However, these events occur too late in the MLC to permit prospective matching for cadaveric renal transplantation. Presentation of allogeneic cells to the T lymphocyte within the MLC results in the emergence of an insulin receptor pharmacokinetically similar to that on other tissues such as fat, liver, and muscle. Intrafamilial MLC were studied by simultaneous assessment of DNA synthesis and insulin receptor binding. In 68 studies from seven families that provide examples of two haplotype identical matches, haplo-identical matches and total haplo mismatches, the presence of an insulin receptor correlated in every case with a positive MLC as estimated by [3H]thymidine incorporation. A quantitative relationship existed between the strength of the MLC and the amount of receptor binding. Based on analysis of cells from several families in which crossover events were known to have occurred, the appearance of an insulin receptor always corresponded with a mismatch at the portion of histocompatibility leukocyte antigen (HLA) chromosome bearing the D region. Finally, it was demonstrated in each of 30 cultures that insulin receptor emergence occurred significantly before detectable DNA synthesis, as early as 24 h after the initiation of the MLC, well within the time-constraint limitations for renal preservation. Appearance of the insulin receptor on activated lymphocytes may be a more rapid measure of mixed lymphocyte responses, and should permit prospective matching for cadaveric renal transplantation.

Cadaver↗
PubMed1981

The absence of cryptic insulin receptors on resting lymphocytes.

Previous experiments have demonstrated that insulin receptors emerge upon stimulated lymphocytes while resting lymphocytes lack insulin receptors. The appearance of insulin receptors is totally dependent on RNA and protein synthesis. The results suggest that insulin receptors are synthesized de novo or that new protein is synthesized that is responsible for activation of the receptor. In this study, we investigated the possibility that cryptic membrane receptors are present before lymphocyte activation. As a precedent, hypertonic salt solutions or enzymatic digestion have been reported to uncover cryptic insulin receptors in liver and fat cell membranes. Similar treatment of lymphocytes failed to reveal cryptic, stereospecific receptor sites, although nonspecific insulin binding did increase.

Animals↗
PubMed1981

The parallel, time-dependent, bimodal change in lymphocyte cholinergic binding activity and cholinergic influence upon lymphocyte-mediated cytotoxicity after lymphocyte activation.

The potent muscarinic cholinergic antagonist 3-quinuclidinyl benzilate has been used to detect muscarinic acetylcholine receptors on rodent and human lymphocytes. Binding to B lymphocytes was minimal and was not saturable or ligand specific. Half-maximal binding of (3H)-quinuclidinyl benzilate to T lymphocytes occurred at concentrations comparable to those described in other systems, and was displaceable at physiologic concentrations by muscarinic but not nicotinic agonists and antagonists. Binding to T lymphocytes was both saturable and specific, and was found to rapidly increase significantly after mitogen activation. Activation of T lymphocytes or the Lyt 1+ subset produces an early increase and later fall in muscarinic binding, and the ability od cholinergic agonists to augment the effector function of cytotoxic T lymphocytes harvested from alloimmune rat spleen is directly related to the magnitude of muscarinic binding.

Animals↗