Lymphocyte responses to mitogen stimulation were studied in healthy hemophiliac patients. To study kinetics and dose response, three different concentrations of the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM) were used, and proliferation was measured on each of 6 days. Patients with T4/T8 ratios of less than 1.00 showed decreased proliferation compared to normal controls and to hemophiliac patients with ratios greater than 1.00. These findings were more pronounced with PWM than with PHA. Over the range of concentrations tested, patients and controls showed similar dose responses to PHA; no dose responses to PWM were demonstrable. There were no significant differences among the patient and control groups in kinetics of response to either mitogen. Interleukin-II (IL-2) activity produced in response to PHA stimulation also was studied. Hemophiliac patients with T4/T8 ratios less than 1.00 showed decreased IL-2 activity in 48-hour PHA culture supernatants compared to normal controls and hemophiliac patients with ratios greater than 1.00.

Adolescent↗

PubMedDate not supplied

Reversal of graft-versus-host disease with infusion of autologous bone marrow.

Graft-versus-host disease (GVHD) remains a major complication of bone marrow transplantation. This report describes reversal of GVHD by infusion of stored recipient bone marrow following combined liver-bone marrow allotransplantation. Graft-versus-host disease developed at the end of the first postoperative week. The skin involvement progressively spread to approximately 80% of the body surface and was not affected by modification of the immunosuppressive treatment. On the 42nd and 43rd postoperative day 1.23 x 10(8) and 1.6 x 10(8) autologous bone marrow cells per kg of recipient body weight were infused. The skin rush began to dramatically improve and resolved within 2 wk from the autologous marrow infusion. Autologous bone marrow storage previous to allogeneic bone marrow transplantation for tolerance induction could constitute a safety net in case of occurrence of GVHD.

Biopsy↗

PubMedDate not supplied

Interleukin-6, a marker of preservation injury in clinical lung transplantation.

Interleukin-6 (IL-6) is one of the cytokines produced by human alveolar macrophages, lung parenchyma, and other cells in response to injury and infection. We hypothesized that IL-6 is released from poorly preserved lung grafts and may serve as a marker of preservation injury. Sixteen patients who received lung allografts were enrolled in this study. The average ischemic time was 284 +/- 78 minutes. Serum IL-6 level was measured before and at 4 and 24 hours after reperfusion of the grafts by an enzyme-linked immunosorbent assay. Preservation injury was assessed by (1) the need for prolonged intubation (> 7 days), (2) the arterial/alveolar oxygen tension ratio (PaO2/PAO2 ratio) at 4 hours after graft reperfusion (only in heart-lung or double lung recipients), (3) the presence of diffuse alveolar damage on first lung biopsy, and (4) the 30-day graft survival rate. IL-6 level peaked at 4 hours after reperfusion and returned to baseline at 24 hours. The patients were divided into group I (n = 6) and group II (n = 10), depending on whether the 4-hour IL-6 level was more than 1000 pg/ml or less than 500 pg/ml, respectively. Group I patients required longer intubation (p < 0.01) and had a lower PaO2/PAO2 ratio (p < 0.001), more diffuse alveolar damage (p < 0.01), and a lower graft survival rate (p < 0.01) than those of group II. No bacterial, fungal, or viral infection was found during postoperative week 1 in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Presence of CD4, CD8 double-negative and T-cell receptor-gamma-delta-positive T cells in lymphocyte cultures propagated from coronary arteries from heart transplant patients with graft coronary disease.

Previous studies have shown that the interleukin-2-induced propagation of lymphocytes from endomyocardial biopsy specimens, an indicator of cellular rejection, is associated with the development of graft coronary disease in heart transplant patients. To further investigate the concept of cell-mediated immune responses in graft coronary disease, we have applied the methodologies of interleukin-2-induced propagation of lymphocytes from arterial tissues. In a group of 23 patients, which included 6 heart, 6 kidney, and 11 liver transplant recipients, we observed that arterial lymphocyte growth was significantly associated with obliterative vasculopathy (p less than 0.03). T-cell phenotyping analysis of coronary artery-derived lymphocyte cultures from three heart transplant patients with graft coronary disease showed significant numbers of CD4, CD8 double-negative T cells and T-cell receptor-gamma delta cells, especially when the cultures were established with relatively high doses of 400 U/ml of interleukin-2. These data suggest that the subset of CD4-CD8-, T cell receptor-gamma delta+ T cells may play a role in the pathogenesis and progression of graft coronary disease.

CD4-CD8 Ratio↗

PubMedDate not supplied

Monoclonal versus polyclonal antibody therapy for prophylaxis against rejection after heart transplantation.

Between August 1986 and December 1987, 88 patients received either RATG or OKT3 for immunoprophylaxis before heart transplantation. By the end of the first month after transplantation, 25% of the patients who received RATG had experienced a rejection episode compared with 43% of those receiving OKT3. This difference was persistent as many as 4 months after transplantation. While 50% of the OKT3 patients had a second episode of rejection, only 35% of the RATG patients did so. Randomization of these agents was complicated by severe cardiopulmonary side effects attributed to the first dose of OKT3. Five hours after the first dose of OKT3, a 25% drop in mean arterial pressure, accompanied by significant hypoxia, was seen in a majority of patients. There was no difference in the incidence of infection between the two groups.

Antibodies, Monoclonal↗

PubMedDate not supplied

Lymphocyte growth from cardiac allograft biopsy specimens with no or minimal cellular infiltrates: association with subsequent rejection episode.

Histologic features of endomyocardial biopsy specimens are essential in the monitoring of heart transplant patients. Significant cellular infiltrates accompanied by myocyte damage are diagnostic of transplant rejection, whereas no or minimal infiltrates (grades 0 and 1) suggest absence of rejection. Biopsy specimens were cultured on the basis of the principle that the allograft is infiltrated by activated lymphocytes, which can be expanded in the presence of interleukin-2, a lymphokine that induces proliferation of activated T cells. Although frequency of cell cultures was proportional to histologic rejection grade, 39% of biopsy specimens with grades 0 and 1 cultured during the first month posttransplantation yielded lymphocyte growth. Cell growth was observed in 28% of biopsy specimens with grades 0 and 1 obtained during the first 10 days posttransplantation. In this group (growers) 73% showed clinical rejection after 9.8 +/- 5.0 days. In contrast, 55% of nongrowers were treated for rejection after 19.1 +/- 13.8 days. For biopsy specimens obtained 11 to 20 days posttransplantation, subsequent rejection episodes were observed in 61% of growers, but in only 33% of nongrowers. For biopsy specimens obtained 21 to 30 days posttransplantation the incidence of clinical rejection was 60% versus 14%, respectively. A sequential analysis of biopsy specimens obtained during the first month posttransplantation enabled us to identify 16 persistent nongrowers; only 6 (37%) experienced clinical rejection during the first 3 months posttransplantation. Most of the persistent nongrowers were found among patients on the immunoprophylactic rabbit antithymocyte globulin protocol. These data suggest that in vitro cultures of biopsy specimens with no detectable or minimal cellular infiltration may be useful in identifying patients at risk of developing rejection.

Adult↗

PubMedDate not supplied

Lymphocytes of bronchoalveolar lavages from heart-lung transplant recipients.

Bronchoalveolar cells from 13 lavages done in six heart-lung transplant recipients were tested for spontaneous proliferation, Interleukin-2 response and secondary allogeneic proliferation measured by primed lymphocyte testing. In most instances the bronchoalveolar cells responded to Interleukin-2 suggesting the presence of activated T-cells in the lavage. The lavage cells from several patients exhibited primed lymphocyte testing responses suggesting the presence of alloreactive T-cells. A high degree of spontaneous cellular proliferation was observed in several lavages, which appeared to be due to a macrophage-lymphocyte reaction. Two mechanisms may be responsible for this reactivity; a macrophage-lymphocyte reaction as a result of recipient lymphocyte responses to donor macrophages in the lavage during the early post-transplant period, or a macrophage-lymphocyte reaction related to an ongoing infection. Thus, functional assays on bronchoalveolar lavage cells may have diagnostic value in monitoring heart-lung recipients for lung rejection and infection.

Bronchi↗

PubMedDate not supplied

HLA phenotype of lung lavage cells following heart-lung transplantation.

A transplanted lung contains a full complement of immunocompetent lymphocytes and macrophages that are able to react immunologically with recipient lymphocytes and macrophages. In this study, the origin of lymphocytes and macrophages recovered from sequential bronchoalveolar lavages of six heart-lung transplantation recipients was determined by histocompatibility phenotyping. We found that during the first four weeks after transplantation there is a rapid replacement of the donor cells with those of the recipient. Since lung rejection rarely occurs after this transition is complete, donor lymphocytes and macrophages may be an important component of the rejection process. Furthermore, the transition from donor to recipient phenotype indicates that the vast majority of human alveolar macrophages originate from bone marrow precursors.

HLA Antigens↗

PubMedDate not supplied

Heat shock protein-induced T-lymphocyte propagation from endomyocardial biopsies in heart transplantation.

BACKGROUND: Recent studies have shown that heat shock proteins can be recognized by T cells during various immunologically mediated inflammatory processes. Injurious stimuli to cells induce an increased production of heat shock proteins which could lead to their cell surface expression and subsequent recognition by the immune system. We have postulated that allograft infiltrating cells may recognize heat shock proteins, especially during rejection. METHODS: This hypothesis was tested by incubating heart transplant biopsy specimens from 89 heart transplant recipients with soluble Mycobacterium tuberculosis extracts, a source of heat shock proteins or recombinant mycobacterial heat shock protein 65. T cell phenotypes were determined by flow cytometry. RESULTS: Mycobacterium tuberculosis extract can induce lymphocyte propagation from heart transplant biopsy specimens especially during rejection. A highly significant correlation was seen between Mycobacterium tuberculosis extract and interleukin-2-induced lymphocyte growth and an accelerated growth was seen for cultures incubated with Mycobacterium tuberculosis extract + interleukin-2. A second series of experiments has also shown the propagation of lymphocytes induced by recombinant mycobacterial heat shock protein-65. T-cell phenotype analysis of biopsy propagated lymphocytes has shown higher frequencies of CD8 cells in Mycobacterium tuberculosis extract and heat shock protein-65 propagated lymphocytes from early posttransplantation biopsy specimens, whereas, later on, most cultures showed a predominance of CD4 cells. T-cell receptor gamma delta cells were more frequently found in biopsy-derived lymphocyte cultures from long-term survivors, especially after propagation with Mycobacterium tuberculosis extract and heat shock protein-65. These gamma delta cells expressed primarily the delta 1 rather than the gamma 9 phenotype. CONCLUSIONS: These observations provide first evidence for the presence of heat shock protein-reactive lymphocytes in cellular infiltrates of transplants undergoing rejection.

Adult↗