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Studies on the leukocytosis and lymphocytosis induced by Bordetella pertussis. 3. The distribution of transfused lymphocytes in pertussis-treated and normal mice.

Peripheral blood lymphocytes were isolated from normal mice and mice undergoing pertussis-induced lymphocytosis. After labeling in vitro with tritiated uridine the cells were transfused into normal or pertussis-treated mice. It was found that the lymphocytes from pertussis-treated mice entered the lymph nodes of both normal mice and pertussis-treated mice to a significantly lesser extent than did normal lymphocytes which had been transfused into either class of recipient. In addition, an interdependence of changes in the various body compartments examined was found when normal lymphocytes were injected into either type of recipient. However, when pertussis lymphocytes were injected into normal mice there was no interrelationship between the changes in the node with those in the blood, liver, lung, or spleen. In the case of pertussis lymphocytes transfused into pertussis-treated mice no interrelationship between any two compartments was observed. It was concluded that in pertussis-treated mice there is an inhibition of lymphocyte emigration which is primarily the consequence of an effect on the cell.

Animals↗

Lymphocyte transfusion in recent onset type I diabetes mellitus--a one-year follow-up of cell-mediated anti-islet cytotoxicity and C-peptide secretion.

In 19 patients with newly diagnosed Type I diabetes mellitus a single transfusion of 1.9 x 10(9) to 1.5 x 10(10) lymphocytes was performed. Fifteen Type I diabetic patients who did not receive a transfusion were used as controls. Anti-beta-cell cell-mediated cytotoxicity was measured using an insulin release assay. Stimulated C-peptide secretion (100 g glucose orally, 1 mg glucagon i.v.) was used to estimate residual beta-cell function. Both parameters were measured prior to transfusion and after 12 months. The transfusions were followed by a fall of cytotoxicity below the 95% confidence limit of the controls in 11 of the 19 patients ('responders') (15.7 +/- 1.7 ng insulin/islet/20 h vs 6.7 +/- 1.3 P less than 0.001), while the other eight transfused patients ('non-responders') (13.5 +/- 1.9 vs 17.1 +/- 2.9, ns) and the non-transfused control patients (11.6 +/- 1.1 vs 14.2 +/- 2.4, ns) displayed persistently high cytotoxicity levels. In the responder group a slight improvement in stimulated C-peptide secretion was observed (136 +/- 43 pmol/dl vs 148 +/- 38, ns) whereas in the non-responder (127 +/- 28 vs 106 +/- 25, ns) and in the control group (130 +/- 17 vs 97 +/- 19, P less than 0.05) the stimulated C-peptide responses declined during the 12-month follow-up. Thus, lymphocyte transfusion may have beneficial effects by suppressing anti-beta-cell cytotoxicity and preserving C-peptide secretion.

Adolescent↗

The effect of neuraminidase on the fate of transfused lymphocytes.

Evidence has been obtained that incubation of rat lymphocytes with neuraminidase, prior to intravenous transfusion into allogeneic or syngeneic recipients, alters the distribution of the cells. Many enzyme-treated lymphocytes initially become trapped in the liver, and there is a decrease in the selective accumulation of these cells in the lymph nodes and spleen. Subsequently, many enzyme-altered cells emigrate from the liver, concentrate in lymph nodes, and recirculate to the lymph. The results suggest that sialic acid constituents of the lymphocyte surface play a critical role in ensuring the normal distribution of these cells in the body. The findings also imply that reactions involving surface sialic acid can markedly alter the fate of lymphocytes without "killing" the cells.

Agglutination↗

Kinetics and organ distribution of allogeneic natural killer lymphocytes transfused into patients suffering from renal cell carcinoma.

The transfusion of natural killer (NK) lymphocytes into patients suffering from malignant diseases is an approach of current interest in the field of immunotherapy. Little is known about the organ distribution, survival, and clearance of donor immune effector cells in cellular therapy, and no reports exist on these important parameters considering NK cells in particular or any other type of allogeneic lymphocytes in humans. In the context of a clinical Phase I/II study we examined the distribution of transfused allogeneic NK cells in patients suffering from renal cell carcinoma. The NK cells were ex vivo cultivated and activated before transfusion. To assess the circulation of the transfused cells in the peripheral blood, we used a nested PCR technique to detect HLA DRB1 alleles of the NK cell donors. Post-transfusion, all patients showed evidence of circulating donor cells for up to 3 days. After 7 days, all donor cells were cleared from the blood to undetectable levels. To assess organ distribution, (111)In-labeled NK cells were injected and monitored by whole-body scintiscans. A distribution to the whole body, with preference for liver, spleen, and bone marrow, was observed after a short initial uptake in the lungs. No activity was observed in lymphatic nodes. A total of 2/4 evaluable metastases showed a clear accumulation of transfused NK cells. The half-life corrected activity in all body compartments remained almost constant over the 6-day observation period in concordance with the absence of any excretion of radioactivity. This may indicate an extended survival of the transfused cells, despite their foreign nature, in the host organism.

Carcinoma, Renal Cell↗

Timing of lymphocyte transfusion and portal clamping for the development of lethal graft-versus-host disease in the rat.

The effects of surgical intervention on the incidence and augmentation of graft-versus-host disease (GVHD) were studied in the rat. To elicit GVHD, splenocytes from parental LEW rats at a dose of 4 x 10(8) or 1.5 x 10(8) cells/350g body weight were injected via the tail vein into (LEW x BN)F1 rats. The injection of 4 x 10(8) of LEW rat splenocytes induced lethal GVHD in all nontreated F1 rats, while 1.5 x 10(8) of LEW splenocytes did not induce any signs of GVHD. However, when the F1 rats had received the same dose of parental LEW lymphocytes in combination with portal clamping, 14 recipients out of the 15 rats (93%) suffered GVHD and 10 rats (67%) died from GVHD. Interestingly, portal clamping 7 days after the injection enhanced the incidence of GVHD, whereas no GVHD was observed in the intervention group either 3 or 7 days prior to the cell transfusion. When 1.5 x 10(8) of allogeneic lymphocytes were injected intravenously together with 0.1-1.0 mg/kg of endotoxin instead of portal clamping, the injection led the early death by GVHD, while the injection of methylpredonisolone did not enhance GVHD. These results thus indicate that either simultaneous or delayed surgical intervention has the potential to trigger a dormant state in transferred alloreactive lymphocytes.

Animals↗

Lymphocyte transfusions prevent diabetes in the Bio-Breeding/Worcester rat.

The Bio-Breeding/Worcester (BB/W) rat develops spontaneous autoimmune diabetes similar to human insulin-dependent diabetes mellitus. Transfusions of whole blood from the nondiabetic W-line of BB/W rats prevent the syndrome in diabetes-prone recipients. We report three experiments designed to determine which blood component is protective. In all experiments, diabetes-prone BB/W rats 23 to 35 d of age were given four or six weekly intravenous injections. In the first experiment, animals received either saline or transfusions of erythrocytes, white blood cells, or plasma from W-line donors. Diabetes occurred in 7/22 (32%) erythrocyte, 2/27 (7%) white cell, 14/24 (58%) plasma, and 15/27 (56%) saline recipients (P less than 0.001). At 120 d of age, peripheral blood was obtained from nondiabetic rats. Fluorescence-activated cell sorter analysis of OX 19 tagged leucocytes revealed 35% T lymphocytes in white cell recipients (n = 13), compared with 9% in saline recipients (n = 7; P less than 0.001). Responsiveness to concanavalin A was also increased in the white cell group, whereas the frequency of both insulitis and thyroiditis was decreased. In the second experiment, 1/19 (5%) rats transfused with W-line spleen cells developed diabetes, as contrasted with 12/18 (67%) recipients of diabetes-prone spleen cells and 19/31 (61%) noninjected controls (P less than 0.001). In the third experiment, diabetes-prone rats received either W-line blood treated with a cytotoxic anti-T lymphocyte antibody plus complement, untreated blood, or saline. Diabetes occurred in 8/20 (40%), 1/20 (5%), and 13/19 (68%) rats in each group, respectively (P less than 0.001). We conclude that transfusions of W-line T lymphocytes prevent diabetes in the BB/W rat.

Animals↗