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T B Strom

Publications and source records attributed to T B Strom.

At least 271 records · Page 15Linked to original sources
PubMed1984

Cloned human interferon-gamma, but not interferon-beta or -alpha, induces expression of HLA-DR determinants by fetal monocytes and myeloid leukemic cell lines.

The antigen presenting function of macrophages and other accessory cells requires the cell surface expression of class II major histocompatibility antigens, e.g., HLA-DR. It has been shown that gamma-interferon (IFN-gamma), a T cell product, can regulate macrophage HLA-DR expression. The effect of absolutely pure or cloned IFN-gamma upon fetal monocytes that do not strongly express DR has not been studied. We have utilized cloned IFN-gamma, IFN-beta, and IFN-alpha preparations to examine the differential effects of these molecules upon the expression of HLA class I (HLA-A,B) and class II determinants by fetal monocytes as well as by myeloid leukemic cell lines. We report that cloned human IFN-gamma induces the expression of HLA-DR and -A,B antigens on cells that normally express low quantities of these molecules, including human fetal monocytes and two (ML-1 and HL-60) but not a third (U-937) myeloid leukemic cell lines. These findings suggest that the acquisition of class II HLA molecules upon fetal tissues and perhaps antigen presenting function is dependent upon IFN-gamma. In contrast, IFN-beta and -alpha induced the expression of HLA-A,B but not HLA-DR antigens by these cells. Thus, these data indicate that the expression of HLA-DR molecules that is vital for monocyte/macrophage and T cell interaction is stimulated by the lymphokine IFN-gamma, and that the effects of IFN-gamma are distinctive from IFN-alpha or -beta.

Aging↗
PubMed1983

Simultaneous flow cytometric analysis of human T cell activation antigen expression and DNA content.

Cell-surface antigens that are induced to appear on T cells activated by the lectin phytohemagglutinin-P (PHA) can be classified both on the basis of the kinetics of their appearance and on their growth-association properties. Seven distinct T cell activation antigens, defined by monoclonal antibodies, were classified as early, intermediate, or late antigens based on their temporal appearance relative to DNA synthesis. Four antigens, the transferrin receptor, the T cell activation antigen Tac, the 4F2 antigen, and the 49.9 antigen were early antigens, whereas the OKT10 antigen appeared at intermediate times and both HLA-DR and antigen 19.2 appeared late. The use of a dye, Hoechst 33342, which stains DNA stoichiometrically, allowed the simultaneous analysis of immunofluorescence and cell cycle position of individual cells. This analysis unexpectedly revealed that essentially all cells in the proliferative phase of the cell cycle expressed each of the four early-activation antigens. The correlation between expression of the four early-activation antigens and T cell proliferation suggests that these molecules are important for the growth of all T cells. The relationship of two of these activation antigens, known to be the receptors for transferrin and interleukin 2, a T cell growth factor, is discussed with special reference to the roles of their ligands in supporting the growth of T cells.

Antibodies, Monoclonal↗
PubMed1983

Immunofluorescence measurement in a flow cytometer using low-power helium-neon laser excitation.

Helium-neon lasers are economical and efficient light sources; their utility in flow cytometry to date has been limited by the lack of fluorescent probes that can be excited at 633 nm. Allophycocyanin (APC), a highly fluorescent phycobiliprotein, can be used as an antibody label and has spectral characteristics suitable for use with He-Ne lasers; we undertook to resolve whether a low-power (7 mW) He-Ne laser could provide sufficient excitation to permit flow cytometric detection of APC-labeled antibodies on cell surfaces. We made an APC conjugate of monoclonal antibody 4F2, which reacts with an antigen abundant on the surfaces of activated human T-lymphocytes; APC-4F2 was used to stain blood mononuclear cells that had been cultured with and without phytohemagglutinin (PHA). Cells so stained were examined in a flow cytometer with orthogonal illumination at 633 nm from a 7 mW He-Ne laser; antibody-bearing cells were detectable by fluorescence emission above 665 nm. Cells from the same cultures were stained with fluorescein-labeled 4F2 antibody and examined in a flow cytometer with argon ion laser excitation at 488 nm. Percentages of antibody-bearing cells determined from APC fluorescence and from fluorescein fluorescence were in good agreement. It thus appears that He-Ne lasers and APC-antibodies are usable for immunofluorescence measurements; the sensitivity attainable with this technique remains to be determined.

Animals↗
PubMed1983

Inhibition of the production of a soluble helper mediator by cyclosporin A results in the failure to generate alloreactive cytolytic cells in mixed-lymphocyte culture.

The mechanism of action of cyclosporin A (CsA) in inhibiting the induction of alloreactive cytolytic T lymphocytes (CTL) in mixed-lymphocyte culture (MLC) was investigated. CsA at concentrations of 10(-3) to 10(-1) micrograms/ml completely prevented the generation of CTL. However, the addition of culture supernatants from mitogen-activated lymphocytes to MLC not only significantly reversed the suppressive effect of CsA but also fully restored the reactivity of lymphocytes already treated with CsA. By measuring the presence of a soluble helper mediator (SHF) in MLC supernatants, we found that CsA-treated lymphocytes produced no SHF, possibly interleukin 2 (IL-2). The effect of CsA on receptors for IL-2 was subsequently studied and it was found that the binding capacity of 125I-labeled IL-2 to lymphocytes was not altered by the presence of CsA. These findings suggest that the prevention of helper cells from producing SHF, rather than the inhibition of the response of effector cells to SHF, is a possible explanation for the immunosuppression mediated by CsA.

Animals↗
PubMed1983

Transplantation: immunogenetic and clinical aspects--part II.

The ultimate goal is not merely to find a better way of treating acute rejection; efforts are now concentrated on prophylactic immunosuppression with low-dose regimens of azathioprine and steroids. In the wings is cyclosporine, a fungal polypeptide that shows great promise in clinical trials. And on the horizon there is hope that monoclonal antibodies may hold the key to prevention.

Adult↗
PubMed1983

Prostaglandin as an effective antirejection therapy in rat renal allograft recipients.

Because adenylate cyclase activators such as prostaglandin E1 elevate lymphocytic cyclic AMP and inhibit T cell proliferation and the effector function of cytotoxic T cells in vitro, we tested the efficacy of 15(S)-15-methyl prostaglandin E1, a prostaglandin derivative with a prolonged biologic half-life. Treatment with this agent resulted in a near complete protection of renal grafts from immunologic damage, despite withholding therapy until day 4 following transplantation.

Alprostadil↗
PubMed1983

Long-term renal allograft survival in rats preimmunized with donor strain RT1.B antigens.

Rat renal allograft survival was enhanced by active immunization with donor strain RT1.B (Ia) antigens. Lewis (LEW) rats (16) were immunized with Brown Norway (BN) lymphocyte extracts containing RT1.B, but not RT1.A antigens, prior to receiving (LEW X BN)F1 renal allografts. Group 1 (8 rats) was immunized with lymphocyte membrane fragments group 2(8 rats) was primed with lymphocyte supernatant extract. Longterm survivors (greater than 60 days; 12 animals) had a mean blood urea nitrogen of 75 +/- 31 mg% and serum creatinine of 2.0 +/- 0.8 mg% at one month. Death occurred in 90% of control allograft recipients within 10 days. Anti-BN RT1.B but not RT1.A antibodies were detected in sera from actively enhanced rats following immunization and at day 7 posttransplantation. We conclude that preimmunization with cell extracts containing donor RT1.B antigens has a protective effect on the allograft, and that the phenomenon of active immunologic enhancement can be produced without immunization to RT1.A antigens.

Animals↗
PubMed1983

Restoration of allograft responsiveness in B rats. II. Requirements for lymphoid populations and lymphokine.

B rats, produced by lethal x-irradiation of thymectomized animals that are then reconstituted with bone marrow cells from syngeneic, thymectomized, and thoracic-duct-drained donors, are unable to reject histoin-compatible heterotopic cardiac allografts. In these studies, we have continued to investigate the role of immune competent cells and lymphokine in restoring acute allograft rejection in these animals, noting that adoptive transfer of 10(8) sensitized splenocytes (sSL) plus Interleukin-2-rich conditioned medium, IL-2 (CM) will reproducibly produce acute responsiveness toward long-standing, well-functioning, heart grafts. We have now noted that sensitized lymph node cells or thoracic duct lymphocytes can also reverse the unresponsive state, with IL-2 rich conditioned supernatants increasing the effectiveness of small numbers of cells from these populations in inducing allograft rejection. Furthermore, the major cellular components within the spleen have been separated using antibody techniques, and their individual role in the rejection reaction has been assessed. Although 10(8) sSL plus IL-2 (CM) can produce acute rejection in a time comparable to that occurring in unmodified recipients (n = 20, MST +/- SD = 8.4 +/- 1.3 days), neither the T cell fraction (6 x 10(7] of 10(8) SL + IL-2 (CM) (n = 10, MST +/- SD = 17.4 +/- 7.3 days), nor addition of the adherent cell fraction to the T cell component (MST +/- SD = 18 +/- 2 days) or addition of the B cell fraction (MST +/- SD = 15.5 +/- 2.1 days) could restore acute responsiveness. However, increasing the numbers of T cells to 10(8) and transferring concomitantly with IL-2 (CM) again produced acute rejection (n = 4, MST +/- SD = 9 +/- 1.1 days). These data suggest that T cells form the essential element of transfer in the B rat, although other cells present in SL appear necessary to provide an optimal milieu. Our experiments also suggest that this response is independent of the route of administration or of higher doses of IL-2. Finally, using a dual allograft model, it appears that graft destruction is determined by the specific sensitivity of transferred SL; IL-2 (CM) being a nonspecific factor in the response.

Animals↗
PubMed1983

Treatment of acute renal allograft rejection with monoclonal anti-T12 antibody.

Nineteen patients with acute rejection of a renal allograft were treated with the monoclonal antibody anti-T12, directed against a determinant present on all post-thymic T cells. Seven patients had a good response, four had an equivocal response, and eight failed to respond. Histologic studies demonstrated that the good responders had primarily cellular rejection. The nonresponders included 4 patients with moderate-to-severe humoral rejection, one patient with an inadequate dose of antibody, one patient who withdrew before completing the study, and one patient with late end-stage rejection. All eleven patients with good or equivocal responses have functioning kidneys in a follow-up of 1-15 months (mean 7 months). Only one patient has had a subsequent acute rejection episode, which responded to a steroid pulse. No significant complications of anti-T12 therapy occurred.

Adult↗
PubMed1983

Monoclonal anti-T12 antibody as therapy for renal allograft rejection.

Nineteen renal allograft recipients experiencing rejection were infused with monoclonal mouse anti-human T12 directed to a T lymphocyte differentiation antigen expressed on mature post-thymic cells. Patients were offered this therapy as an alternative to high-dose methylprednisolone after diagnosis of an acute rejection episode within 3 months of transplantation. Seven patients had clear-cut reversals of rejection activity within the 10-day period of treatment. Four additional patients had delayed responses in association with acute tubular necrosis and/or cyclosporine toxicity, and they received other therapies according to protocol when anti-T12 alone had not caused a response after 5 days. All but one of these responding patients have been free of subsequent acute rejection over a 1-15 month follow-up period. Treatment failures appear to be related to the presence of allo-antibody-mediated vasculitis. Therapy was well tolerated. These preliminary studies have revealed the existence of a T12 negative subpopulation of extrathymic T cells, usually undetectable in peripheral blood.

Antibodies, Anti-Idiotypic↗
PubMed1982

The improving utility of renal transplantation in the management of end-stage renal disease.

The results achieved by treating patients with end-stage renal failure with allotransplantation have improved dramatically since the 1950s when immunosuppression was induced by total body irradiation and there was a lack of HLA typing. Although long-term hemodialysis offers prolonged survival and partial rehabilitation for many individuals with end-stage renal disease, the technique is inconvenient and time consuming. Patients are restricted by necessary proximity to the machine, dietary limitations, potential failure of access sites, and complications of various organ systems. Despite the availability of dialysis and the federal funds to partially pay for treatment, long-term dialysis still remains a costly process for the individual in need of care. During the same period when dialysis techniques improved and became widely available, transplantation of the human kidney became an established and justified treatment for some patients with end-stage renal disease. Those with successful kidney allografts may achieve remarkable recovery and are often able to return to normal lives. One of the more striking improvements in the results of renal transplantation in recent years had been the decline in morbidity and mortality. Mortality by the end of the first year after transplantation during which time most deaths occur, is currently less than 5 percent in a number of major medical units. In part, this decline represents a change in philosophy by transplant teams, who now tend to decrease immunosuppression and sacrifice the kidney rather than the patient in instances of inexorable rejection. In addition, declining mortality is directly attributable to improved methods of preventing, discovering, and treating patients with potential or real infections. More recently, in some centers, the rate of successful engraftment has shown gratifying improvement due to refinements in tissue typing, improved cross matching, new immunosuppressive therapies, and pretransplant conditioning with blood products. These recent improvements are the primary focus of this review. Unfortunately, until very recently, rates of functional survival of allografts have not been satisfactory.

Adolescent↗
PubMed1982

Conditioned media from activated lymphocytes maintain sympathetic neurons in culture.

Nerve growth factor (NGF) is vital for the development and maintenance of sympathetic neurons. In the present report, we demonstrate that NGF maintenance activity can be substituted by lymphoid cells. Indeed, coculturing lymphoid cells with sympathetic neurons in the absence of exogenous NGF resulted in neuronal survival, as measured by morphological and biochemical criteria. In addition, conditioned media from concanavalin A-activated lymphoid cells could replace NGF. The lymphoid secreted factor differs from NGF in its inability to induce neuronal differentiation, and in its lack of cross-reactivity with NGF in radioimmunoassays. We thus discovered a potential novel source for a factor essential for neuronal survival.

Animals↗
PubMed1982

Cerebromeningitis in immunosuppressed recipients of renal allografts.

The experience with cerebromeningitis in recipients of 769 renal allografts occurring over a 20-year period has been reviewed. Eighteen patients developed this complication; an incidence of 2.7%. Clinical manifestations were often subtle, although fever occurred almost universally. Primary risk factors included diabetes mellitus, use of high dose steroids both as maintenance immunosuppression and as treatment for acute rejection, and coincident infections or complications. The responsible organisms were fungi; the overall mortality rate 44%. By recognizing individual patient types who are at potential high risk for this complication, earlier diagnosis and more prompt and aggressive therapy has diminished the mortality dramatically in the last several years.

Adult↗
PubMed1982

Migration patterns of lymphocytes in untreated and immunologically manipulated recipients of organ allografts.

We have investigated the migration patterns of normal LEW rat splenic lymphocytes (SLs) radiolabeled in vitro with [2-3H]adenosine and adoptively transferred i.v. into LEW hosts bearing LBNF1 heterotopic cardiac allografts. Twenty-four hours after cell transfer, the animals were killed and the radioactivity of all lymphoid and nonlymphoid tissues measured in a beta counter. The following experimental groups were studied: group 1, untreated recipients acutely rejecting their grafts at 7 days after transplantation; group 2, actively and passively enhanced recipients bearing long-term surviving grafts, at 7, 14 to 18, and 25 days; group 3, cyclosporin A-treated recipients; and group 4, B rats, each bearing indefinitely surviving grafts, at 7 and 20 to 30 days. In group 1, 28% of recoverable activity was found in spleen and 22% in mesenteric and peripheral lymph nodes. In animals with well functioning grafts of groups 2 and 3, SLs accumulated in both organs equally (25 to 27%). In animals in group 4, SLs migrated primarily to lymph nodes (30%) and away from spleen (20%). Sequestration in nonlymphoid tissues of animals experiencing graft rejection was higher than those with prolonged or indefinitely surviving hearts. By using mouse anti-rat monoclonal antibodies, the quantitative relationship between T cell subpopulations in transferred cell suspensions and in lymphoid organs of grafted hosts was also assessed. Lymphocyte migration patterns are influenced dramatically by the immunological status of recipients of vascularized organ allografts.

Animals↗
PubMed1982

Late mortality and morbidity in recipients of long-term renal allografts.

The experience of the Peter Bent Brigham Hospital with 217 renal allografts functioning for more than 5 years is reviewed. Patient and graft survival were similar after 5 years, with patient survival being 88 and 66% at 10 and 15 years, respectively, and graft survival 85 and 75% at the same time intervals. Actuarial graft survival at 15 years was higher than patient survival because death with a functioning graft was not considered to be graft failure. No differences in patients or graft survival were found between living related and cadaver donor allografts. There were 33 deaths (15.2%), occurring from 5 1/2 to 20 1/2 years post-transplantation. Chronic liver failure and sepsis were the most common causes of death. Thirty-two patients (14.7%) lost their grafts after 5 years, most commonly from chronic rejection. Another 33 patients (15.2%) had evidence of graft dysfunction secondary to chronic rejection, recurrent glomerulonephritis, ureteral obstruction, or renal artery stenosis. Chronic rejection was generally not responsive to alterations in immunosuppressive medication. Complications of varying severity were common affecting 204 (94%) of the patients. The most frequent were hypertension, cataracts, avascular necrosis, malignancy, urinary tract infection, and pneumonia. These data demonstrate that transplant-related mortality and morbidity continue to occur in recipients of long-term renal allografts. These patients require careful and continuing care in medical centers experienced in transplantation.

Actuarial Analysis↗