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PubMed1986

Passive transfer of experimental allergic encephalomyelitis induced by proteolipid apoprotein.

In an attempt to obtain insight into the pathogenesis of proteolipid apoprotein (PLP)-induced experimental allergic encephalomyelitis (EAE) in Lewis rats (Yamamura et al. 1986), PLP-sensitized lymph node cells or spleen cells were passively transferred into normal or irradiated (400 rad) recipients after incubation with concanavalin A or PLP. Clinical EAE manifested by paraparesis was successfully transferred into irradiated recipients with 2 - 2.5 X 10(8) of the primary cultured cells and histologic EAE could be transferred with as few as 5 X 10(7) cells into naive recipients. This is the first demonstration of passive EAE induced with PLP-sensitized lymphoid cells and suggests the pathogenetic importance of cell-mediated immunity to PLP.

Animals↗
PubMed1994

Edematogenic responses induced by Bothrops jararaca venom in rats: role of lymphocytes.

The intraplantar injection of Bothrops jararaca venom (Bjv) caused an edematogenic response in the rat which was of rapid onset, and reached a peak in about 60 min. The response was markedly attenuated in animals rendered leucopenic by the administration of amethopterin. This inhibition was partially reverted when leucopenic rats were given i.v. suspensions of lymphocytes. Suspensions of neutrophils were ineffective. If the animals were submitted to an experimental obstruction of the thoracic duct, which leads to specific lymphocytopenia, similar inhibition of the edematogenic response was observed. These results suggest that lymphocytes can directly influence the development of the edema induced by Bothrops jararaca venom.

Analysis of Variance↗
PubMed1984

Autostimulatory lymphoid cells in aging mice: induction of syngeneic host-versus-graft reaction by radioresistant adherent cells in normal recipients.

When young (6-week-old) BALB/c and also young C57BL/6 mice were inoculated into footpads with spleen cells from normal, syngeneic, aged donors, their response to the inoculum resulted in the enlargement of popliteal lymph nodes (PLN). The degree of PLN enlargement increased as the age of donor mice increased up to age one year. Spleen and lymph node cell populations were highly effective in eliciting the PLN enlargement. Thymus cells and bone marrow cells were moderately effective, but erythrocytes were ineffective. Resident peritoneal exudate cells and spleen adherent cells were much more effective than a whole spleen cell population. The syngeneic response seems to be attributable to a host-versus-graft reaction, since the PLN response was not affected by 2000 rad irradiation of inoculum cells and since the nylon wool-passed spleen T cell population was ineffective as the stimulator. The response was significantly reduced 3 weeks after thymectomy of recipients. PLN enlargement was also observed in older (7-month-old) mice which received spleen cells of younger mice. In this case, however, the response is ascribable to a graft-versus-host reaction, since the inoculation of radiosensitive spleen T cells into footpads resulted in the PLN enlargement. On the other hand, such a stimulatory activity was not found in either lymph node cells or thymus cells. These results suggest that the antigenicity of adherent cells changes with age and that the change is discernible by spleen-locating and short-lived T cells of young mice.

Aging↗
PubMed1986

The effects of polyinosinic: polycytidylic acid (pI:C) on the GVH reaction: immunopathological observations.

The effects of polyinosinic: polycytidylic acid (pI:C) on the graft-versus-host (GVH) reaction were studied. The drug pI:C rapidly and markedly induces interferon and augments natural killer (NK) cell activity. GVH reactions were induced by injecting parental lymphoid cells intravenously into F1 hybrid mice. The development of a GVH reaction was monitored by measuring the plaque-forming cell (PFC) response to sheep red blood cells (SRBC) and by histological examination. When 30 X 10(6) B6 lymphoid cells were injected into B6AF1 mice, the recipients developed profound immunosuppression by 10-12 days post-GVH induction. In addition, pathological changes indicative of GVH reactions were seen in the spleen, lymph nodes, thymus, liver, lung, pancreas, and salivary gland of these mice. However, the treatment of B6AF1 recipients with pI:C prior to parental cell transfer markedly reduced the degree of suppression of the immune response, as measured by the PFC response to SRBC. Also, such mice failed to demonstrate the histological lesions of GVH disease. Treatment of donor mice with pI:C had no effect in preventing either GVH-induced immunosuppression or pathological changes. This study suggests that a pI:C-induced mechanism, possibly involving NK cells, is capable of regulating the GVH reaction.

Animals↗
PubMed1990

Treatment of metastatic renal cell carcinoma with autolymphocyte therapy. Low toxicity outpatient approach to adoptive immunotherapy without use of in vivo interleukin-2.

Thirty-six patients with Stage IV renal cell carcinoma were treated with autolymphocyte therapy (ALT). This new form of adoptive immunotherapy is based on the infusion of relatively small numbers of autologous lymphocytes that are depleted of suppressor cells and immunized in vitro by a method designed for antigen-specific activation using a 3M KCl extract of autologous tumor and an autologous lymphokine mixture. Patients received six monthly infusions of immunized lymphocytes, all on an outpatient basis. The majority of patients experienced no toxicity. The few reactions that occurred were minor and self-limiting; none required any medical intervention or subsequent delay in therapy. Patients also received oral cimetidine to reduce in vivo suppressor cell function. Survival at twenty-four months is 36 percent. Median survival is fifteen months, a significant improvement over the natural history of this disease. A multi-site, randomized, controlled trial of ALT in renal cell carcinoma has been initiated to confirm that this treatment causes a significant prolongation of survival with virtually no toxicity in these patients.

Adult↗
PubMed1989

Evidence for the in vivo production of interleukin-3 in lethally irradiated mice transplanted with syngeneic murine splenocytes.

We wish to demonstrate new evidence for the in vivo production of interleukin-3 (IL-3). Syngeneic murine splenocytes were transplanted into lethally irradiated mice. The spleen cells in these transplant mice spontaneously produced IL-3 in cultures, and IL-3-like activity was detected in the serum. Chronological changes of the Thy-1 antigen expression on the bone marrow cells, and the number of myeloid progenitors in the bone marrow from post-transplant mice correlated with the amount of IL-3 produced in vivo. These results suggest that IL-3 may be produced by activated T cells during the syngeneic mixed lymphocyte reaction induced in vivo.

Animals↗
PubMed1987

A comparative study of the GVH-R in the chick embryo: effects of various allogeneic cells and various administration routes.

Allogeneic cells inoculated into immunologically immature chick embryos induce a Graft-Versus-Host Reaction (GVH-R), one of the manifestations of which is splenic enlargement. Splenomegaly varies with the composition of allogeneic cell suspensions, route of inoculation and age of recipient embryos at inoculation and autopsy. We have compared the splenomegaly induced by lymphoid cells from spleen or bursa of Fabricius with that induced by peripheral blood lymphocytes, after these cell preparations were either grafted on the chorioallantoic membrane (CAM) at 9 or 13 days or injected intravenously at 13 days. We confirm our previous findings that bursa cells grafted on the 9-day CAM induced splenomegaly as efficiently as other cell preparations. On the other hand, bursa cells did not mediate such an effect after they were injected at 13 days. On the whole, a hierarchy of decreasing efficiency is observed from PBL to spleen and finally to bursal cells. It appears that, as the recipient embryo ages, this hierarchy becomes more marked.

Animals↗
PubMed1979

Suppression of graft-versus-host reaction by preincubation of the graft with an antitumor protein, neocarzinostatin.

The immunosuppressive activity of neocarzinostatin, an antitumor antibiotic with a high molecular weight, was demonstrated, as measured by the local and systemic graft-versus-host reaction in rats. The preincubation of parental strain lymphocytes with doses more than 1 micrograms/ml of neocarzinostatin for at least 10 min at 37 degrees C resulted in the marked suppression of the popliteal lymph node enlargement, when injected subcutaneously into the hind footpads of F1 hybrid rats. The suppressive effect was temperature-dependent and irreversible, because the neocarzinostatin (1 microgram/ml) pretreatment of parental lymphocytes at 4 degrees C was not effective in the suppressive activity, and the reincubation of cells after the removal of the drug from the culture did not result in demonstrable changes in the degree of suppression. The neocarzinostatin pretreatment does not result in visible changes in the oxygen consumption rate and viability of cells in vitro or in the distribution pattern within a regional lymph node, indicating that treated cells may retain the same viability and migration capacity in vivo as do untreated cells. Furthermore, the drug pretreatment resulted in the complete prevention of runting syndrome, when treated parental lymphocytes were injected intravenously into F1 hybrid rats.

Animals↗
PubMedDate not supplied

In vivo augmentation of local xenogeneic graft-versus-host reaction by cimetidine and Bacillus Calmette-Guerin.

Histamine-2 receptor blocker therapy (cimetidine) was combined with nonspecific Bacillus Calmette-Guerin (BCG) immunomoderation in order to obtain a more directed immunostimulatory response. To establish this the local xenogeneic graft-versus-host reaction (XGVHR) was used as objective in vivo parameter. In this placebo-controlled experiment the lymphocytes of inbred Sprague-Dawley rats were transferred intradermally to partially immunosuppressed guinea pigs after treatment with either or both of the test substances. The surface areas of the local XGVHRs were evaluated 48 and 72 h later. The local XGVHRs caused by lymphocytes obtained from rats treated with either cimetidine or BCG alone did not differ significantly from those caused by lymphocytes obtained from placebo-treated rats. Combination therapy, however, resulted in significant augmentation of the local XGVHR, clearly indicating a synergistic effect between cimetidine and BCG. The XGVHR appears to be a satisfactory model for evaluating drug effect on cell-mediated immune reaction in vivo.

Animals↗
PubMedDate not supplied

Levamisole augments roxatidine's immune modulatory effects in the graft-versus-host reaction (GVHR).

Levamisole is known to have anti-anergic properties in immune compromised, but no or only marginal effects in immunologically competent subjects. In this study the possibility that levamisole would act as an 'immunoadjuvant' with roxatidine, a histamine H2 receptor blocker, is explored in healthy animals. Sixteen female, inbred Sprague-Dawley rats acted as lymphocyte donors and were treated for 8 days with either a roxatidine-levamisole combination, or levamisole alone, or roxatidine alone or placebo. Five randomly bred guinea pigs and eight inbred BD IX rats acted as lymphocyte acceptors. The in vivo effects of the four treatment modalities on transferred lymphocytes were expressed as the sizes of the allogeneic and xenogeneic graft-versus-host reactions as well as the radioactivity in each AGVHR. The combination of levamisole and roxatidine significantly augmented the cell mediated immune response in vivo and resulted in the most reactive lymphocytes as indicated by the AGVHR's and XGVHR's. These cells mediated reactions with significantly larger wheals as well as more lymphocyte proliferation in each reaction site than those caused by either levamisole or placebo treatment.

Adjuvants, Immunologic↗
PubMed1984

Allogeneic reactivity of maternal lymphoid cells during the course of gestation. Modifications and sex differences in a local GVH assay.

The immune reactivity of lymphoid cells from pregnant mice was studied during the course of pregnancy in primiparous and multiparous animals either " isopregnant " (male and female of same strain) or " allopregnant " (male and female differing at H-2), using a local GVH assay (CBA lymphoid cells injected into (CBA X A/J)F1 recipients). The findings were as follows: The lymphoid cell number in the para-aortic lymph nodes ( PALN ) was increased at all stages of gestation. The peak occurred in the 2nd week in primiparity and as early as 60 h after fertilization in multiparity. PALN cell alloreactivity was weak at the beginning and higher than normal in the third week of pregnancy. Spleen cell alloreactivity was increased in the second week and decreased in the third week in primiparous compared with multiparous animals. Anti-paternal alloreactivity exhibited by spleen cells of allogestation was decreased (as compared to cells of isogestation ) especially in primiparous mice, particularly in the third week. At this time, the anti-paternal alloreactivity of PALN cells was increased. The influence of the recipient's sex on GVHR intensity was reversed when the cells were obtained from a pregnant donor, becoming stronger in male compared with female hybrids.

Animals↗
PubMed1986

Maternal alloimmune reactions towards the murine conceptus and graft-versus-host reaction (GVHR). I. Priming for anti-paternal GVHR by gestation.

In the H-2 compatible (but minor loci-incompatible) BALB/c-DBA/2 strain combination (both H-2d), intravenous injection of 1.3 X 10(7) BALB/c spleen cells from virgin females into DBA/2 newborn mice less than 18 h old does not result in a significant lethal graft-versus-host reaction (GVHR). A strong GVHR (79% lethal) is induced if the BALB/c donors have been preimmunized to DBA/2. Spleen cells from BALB/c mice pregnant by DBA/2 males are also able to induce a significant, but weaker, GVHR (16% lethal) indicating a cellular priming to paternal antigens by gestation. A significant difference exists between anti-DBA/2 GVH reactivity of spleen cells from primiparous (22% lethal) and multiparous (9% lethal) allopregnant BALB/c mice, indicating that the allogeneic boosters of successive allogestations act more on the target-protective side of immunity than on the target-aggressive one. Sera from allopregnant mice (BALB/c X DBA/2) inhibit the GVHR induced by their own cells, while sera from isopregnant ones (BALB/c X BALB/c) have no effect. Thymectomy performed at 6-wk of age, six weeks before gestation did not significantly modify the maternal reactivity. A similar priming by allogestation in the same strain combination was found for local GVHR (induced in adult F1 hybrids) resulting in higher (+132%, P less than 0.005) stimulation indices and seen to be specific for the paternal strain, the indices induced by the same cells being lower (-35%, P less than 0.05) compared to that induced by cells from virgin BALB/c, when injected into irrelevant F1 hybrids (BALB/c X CBA).

Animals↗
PubMed1986

Maternal alloimmune reactions towards the murine conceptus and graft-versus-host reaction (GVHR). II. Inhibition of priming by placental extracts.

Gestation can induce a priming for a GVHR towards paternal strain antigens, although this priming is significantly lower than the one induced by experimental immunization. A role has been sought for placental substances in decreasing this priming through immunomodulation. BALB/c (H-2d) spleen cells do not usually induce a systemic, lethal GVHR in DBA/2 (H-2d) newborn mice except when the donors are preimmunized with DBA/2 cells. Placental extracts (as well as RPMI medium or liver extracts used as controls) were added to DBA/2 cells injected into BALB/c mice used as cell donors for GVH induction. The latter's spleen cells, harvested on day 6 after immunization, were used for systemic and local GVHR. In the systemic assay (lethal effect on DBA/2 newborn mice injected i.v. with BALB/c spleen cells) a significant protection was observed. In the local assay (popliteal lymph node assay in F1 hybrids injected with BALB/c spleen cells into the foot-pad) a highly significant inhibition of priming was detected in recipients injected with spleen cells from placental extract-treated donors. The stimulation index was even lower than that obtained with unprimed BALB/c spleen cells. The same type of local GVHR in (CBA/Ca X A/J) F1 hybrids injected with CBA cells led to similar results. In both situations (systemic and local GVHR) the observed inhibition was found to be specific to the priming cell strain. These results support the working hypothesis that placental substances are able to modify the systemic response of an organism towards both H-2 and non-H-2 alloantigens.

Animals↗
PubMed1992

Interaction between inoculated allogeneic lymphocytes and fetal rats.

Interaction between allogeneic lymphocytes and 12-20-day gestation rat fetuses was examined in vitro and in vivo. Intravenous injection of lymphocytes was achieved either by in vitro cannulation of the vitelline vein followed by culture of the whole fetus, or of its organs, or by in utero cannulation of the vitelline vein through the uterine wall. Cytotoxic reactions on the part of the inoculated allogeneic lymphocytes against fetal tissue could not be detected in the young hosts. The fetal spleen, mesentery and intestine appeared to have a specific affinity for adult lymphocytes from the earliest gestational age examined.

Animals↗
PubMed1992

The influence of intravenously introduced allogeneic lymphocytes on fetal rats.

Semi-allogeneic or allogeneic bone marrow cells, or allogeneic spleen cells, were injected in utero into PVG, DA and Fischer rat fetuses at 15-18 days of gestation via the vitelline vein. Prenatal (PVG x DA) F1 bone marrow cell inoculation produced allograft tolerance far more frequently in DA recipients than in PVG recipients. Inoculation of allogeneic or semi-allogeneic spleen cells into rat fetuses failed to induce allograft tolerance but sensitized the recipients. The observation that Fischer recipients could be rendered tolerant to skin allografts by prenatal inoculation of PVG, but not DA, bone marrow cells indicated that variation in susceptibility to tolerance induction among different donor-recipient strain combinations is unlikely to be explicable on the basis of strain differences in developmental maturity of the host immune system.

Animals↗
PubMed1984

Immunity to Babesia in mice. I. Adoptive transfer of immunity to Babesia rodhaini with immune spleen cells and the effect of irradiation on the protection of immune mice.

Immunisation of Balb/c mice against Babesia rodhaini by an amicarbalide-controlled infection resulted in a solid immunity which lasted for 216 days. With spleen cells of immune mice protection could be transferred both to naive mice pretreated with cyclophosphamide. Treatment of naive mice with cyclophosphamide (300 mg/kg) five days before a lethal B. rodhaini inoculation resulted in over 50% survival. This protective effect of cyclophosphamide is explained by its inhibiting effect on suppressor T-cells. The protection against B. rodhaini challenge infection afforded to immune Balb/c mice was completely resistant to a sublethal irradiation of 400 rad. Since B-lymphocyte function in antibody production is suppressed by this dose, the role of antibodies in the effector phase of the immunity appears to be of minor if any importance. A considerable degree of protection was still preserved after irradiation of immune animals with 875 rad. Sensitivity to this irradiation dose of all immunocompetent cells except macrophages and a small fraction of T-lymphocytes indicates the involvement of these cell types in the effector phase of the specific immunity. Highly radioresistant macrophages are therefore considered to play the major role but T-lymphocytes are also required for complete protection.

Animals↗
PubMed1986

To compare the incubation period following intratracheal and subcutaneous inoculation of bovine leukosis virus infected lymphocytes and to study their clearance from the circulation.

The migration of fluorescein isothiocyanate labelled lymphocytes through the tracheobronchial mucosa has been studied in cattle. Following intratracheal inoculation of labelled non-infected autologous lymphocytes and bovine leukosis virus (BLV) infected heterologous (presumed allogeneic) lymphocytes, the labelled lymphocytes appeared in the blood circulation between 4 and 7 days post inoculation. Following intravenous inoculation of labelled autologous lymphocytes, the cells could be detected in the circulation for 10 days post inoculation whereas BLV infected and non-infected heterologous lymphocytes could be detected for only 2 days. The migration of BLV-infected heterologous lymphocytes through the tracheobronchial mucosa caused a delay in the appearance of labelled lymphocytes in the circulation and a corresponding delay in the appearance of BLV antibodies. Comparison was made of the effect of two different routes of inoculation, subcutaneous and intratracheal on the incubation period as indicated by the detection of antibody. Subcutaneous inoculation of 1 X 10(4), 5 X 10(3), 1 X 10(3) of lymphocytes from a BLV infected cow caused seroconversion whereas 5 X 10(2) cells did not. Intratracheal inoculation of 5 X 10(3) cells caused sero-conversion. One animal did not develop BLV antibody until 30 weeks after inoculation although BLV could be isolated from the blood at 24 and 26 weeks post inoculation.

Animals↗