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At least 37 records · Page 2Linked to original sources
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↗
PubMed1978

Evaluation of the normal-lymphocyte-transfer test.

The normal-lymphocyte-transfer test has been advocated as a method of assessing the immuno-competence of lymphocytes from patients with breast and large-bowel cancer. Evidence is presented in this paper that the methodology is subject to many uncontrollable errors, that the reaction is the result of multiple factors, and that the size of the reaction is related to the age of the patient and not to the extent of the malignancy.

Adult↗
PubMed1978

Enhancing and inhibiting effects of spleen cells from tumour-bearing mice on growth of virus-induced primary sarcoma.

The effects of adoptive transfer of spleen cells from tumour-bearing mice on the growth of Moloney murine sarcoma virus (M-MuSV)-induced primary tumours in BALB/c mice were studied. The effects were in 2 directions, depending on the time of lymphocyte inoculation; when spleen cells from tumuor-bearing mice 12 days after M-MuSV inoculation were inoculated into recipient mice before M-MuSV inoculation, the appearance of tumours was significantly delayed and their incidence was reduced, whereas when these lymphocytes were inoculated after the development of tumours in recipient mice, tumour growth was significantly enhanced. The data indicated that these inhibiting and enhancing effects were mediated mainly by T cells. The mechanisms of the parodoxical effects were investigated.

Animals↗
PubMed1975

The mechanism of unresponsiveness in lymphocytes specifically selected by antigen in normal rats.

The immunological potentialities of populations of thoracic duct lymphocytes collected from rats recently challenged with sheep erythrocytes were compared with those of lymphocytes from rats immunologically tolerant of this antigen. Both "selected" and tolerant populations fail to mount immune responses to sheep erythrocytes in irradiated syngeneic hosts but can do so if transferred to semi-allogeneic recipients. If co-cultivated with normal lymphocytes in irradiated hosts, both types of population can modulate the responsiveness of the former to sheep erythrocytes. Supplementation of normal lymphocytes with "selected" populations collected earlier than 28 hours after challenge of the donors tends to result in augmented responses while later collections are more likely to be associated with suppression. Consequently, it is suggested that "selected" populations are unresponsive because of the presence of specifically activated cells rather than as a result of their depletion. The influence of "selected" populations on the responsiveness of normal lymphocytes is attributed to this content of activated cells.

Animals↗
PubMed1976

Facilitation of the growth of an allogeneic tumour by suppressor cells in newborn rats.

The intravenous injection of as few as 15 Walker tumour cells into newborn rats consistently resulted in the development of pulmonary metastases and the death of the recipient within 2 weeks. Neither the outcome of tumour cell injection nor the interval until death could be modified by transferring 2 x 10(7) lymphocytes from tumour-immune adult rats to the neonataal hosts. In contrast with this failure to transfer adoptive anti-tumour immune responses to intact recipients, the administration of 350 rad irradiation before transfer of 10(6) immune lymphocytes constantly afforded protection against inoculated tumour cells. The simultaneous transfer of neonatal thymus cells with immune lymphocytes interfered with the establishment of an adoptive response in the irradiated newborn. Intiation of a graft-versus-host response in F1 hybrid neonates by injecting parental strain lymphocytes conferred resistance to tumour growth of the recpient, the magnitude of this effect increasing with the strength of the graft-versus-host reaction.

Animals↗
PubMed1975

Early cellular events in a systemic graft-vs.-host reaction. I. The migration of responding and nonresponding donor lymphocytes.

A systemic graft-vs.-host (GVH) reaction was initiated by the intravenous injection of parental strain thoracic duct lymphocytes (TDL) into irradiated F1 hybrid recipients with in-dwelling thoracic duct cannulae. The migration of the donor lymphocytes was followed by labeling them in vitro with either [3H] or [14C]uridine and measuring radioactivity by scintillation counting of the spleen and lymph nodes of the recipients removed 24 h after injection and in TDL collected throughout this period. The localization of labeled cells was always compared to that of a reference population of nonreactive lymphocytes, e.g. F1 hybrid, labeled with the alternative isotope (Fig. 1). A consistent surplus of the reactive label was found in the spleen which was balanced by a deficit of the reactive label in TDL; lymph nodes gave intermediate values. The same distribution pattern was noted when the reference population was a specifically unresponsive population of the parental strain. This differential distribution depends on recognition of the recipient's Ag-B antigens because when normal lymphocytes were injected together with specifically unresponsive lymphocytes into a "third party" F1 hybrid (against which both populations were reactive) there was no surplus of the normal cells in the spleen and no deficit in the lymph. Moreover in an Ag-B identical strain combination there was no detectable difference in the distribution of reactive and nonreactive populations. The distribution of a labeled reaction population can be accounted for if a substantial minority of cells are immobilized in the spleen and lymph nodes as a consequence of antigen recognition (Fig. 3). When the donor cells in the spleen were assayed 24 h after injection there was paradoxically a slight reduction in their specific GVH activity, which is at least partly because they are under-represented in a single cell suspension. The size of the splenic surplus (23%) and the thoracic duct deficit (12%) suggested that the minority of nonimmune lymphocytes which recognize each Ag-B complex carry 12% of the radioactive label in the original population. It is argued that this provides a near estimate of the frequency of T lymphocytes which can recognize each Ag-B antigenic complex.

Animals↗
PubMed1978

Migratory behavior of lymphocytes with specific reactivity to alloantigens. II. Selective recruitment to lymphoid cell allografts and their draining lymph nodes.

A dual-antigen, dual-isotope assay has been used to monitor the migratory behavior of selectively labeled antiallogeneic lymphocytes in mice challenged subcutaneously in all four foot pads with semiallogeneic spleen cells. 3H-labeled anti-C3H and 14C-labeled anti-C57BL lymphocytes of DBA/2J origin were pooled and adoptively transferred to multiple groups of previously challenged DBA/2J recipients. In some of the studies, separate groups of recipients were challenged with either CDF or BDF spleen cells in all four paws, whereas in others CDF spleen cells were used to challenge the right paws of each mouse in the group and BDF spleen cells to challenge the left paws of each mouse in the group. At intervals varying from 24 to 96 h after challenge, a subgroup of four mice from each appropriate group was sacrificed and the relative numbers of anti-C3H and anti-C57BL lymphocytes present in the challenged paws, draining lymph nodes, and other tissues of each mouse were inferred from the mean 3H/14C ratios of the respective tissues of that subgroup. The results of these studies firmly establish that specific antiallogeneic lymphocytes are selectively recruited to the paws and draining lymph nodes of mice challenged subcutaneously in the foot pads with semiallogeneic spleen cells and are deleted from their circulating blood and nondraining lymph nodes. A mechanism for antigen-induced selective recruitment and its possible functional significance in tumor immunology are discussed.

Animals↗
PubMed1976

Host immune responses after administration of inactivated Venezuelan equine encephalomyelitis virus vaccines. II. Kinetics of neutralizing antibody responses in donors and adoptively immunized recipients.

Lymphoid cell responses to immunization with various formalin-inactivated Venezuelan equine encephalomyelitis (VEE) virus vaccines were monitored in mice by assessment of the development of both the neutralizing antibody response in sera of spleen cell donors and the adoptive neutralizing antibody response induced by spleen cell transfer in recipients. Donors immunized intraperitoneally with formalin-inactivated VEE vaccine (a single dose or a dose on three consecutive days) developed early serum neutralizing antibody responses (larger than or equal to 1:88-1:100) by seven days after immunization. Recipients of spleen cells from such mice were, however, incapable of eliciting a neutralizing antibody response (less than or equal to 1:10). Only spleen cells from donors immunized with inactivated VEE vaccine plus adjuvants (particularly complete Freund's adjuvant and Bordetella pertussis) were consistently capable of producing early, high-titer serum neutralizing antibody responses in adoptively immunized recipients (larger than or equal to 1:50-1:120 on day 4). The magnitude of neutralizing antibody responses of donors to inactivated VEE vaccines did not serve as a useful indicator of whether spleen cells from such mice could adoptively induce antibody responses in recipients. Finally, treatment of immune spleen cells with rabbit antiserum to mouse thymocytes, but not with rabbit antiserum to mouse gamma-globulin or normal rabbit serum, abolished the capacity of such cells to transfer an antibody response adoptively.

Adjuvants, Immunologic↗
PubMed1977

Allogeneic and semiallogeneic immunizations with a strong transplantation antigen (Ag-B).

A comparison has been made between the alloantibody response evoked by graded doses of cells being allogeneic and semiallogeneic with the host. The responses were measured by hemagglutination and complement-dependent lymphocytotoxicity. In the strain combination of rats used (DA leads to HO), a marked difference in the optimal dose was found after i.v. injection of lymphocytes. Although semiallogeneic cells gave the better antigenic stimulus at lower cell doses (0.3 and 3 X 10(6) cells), allogeneic cells were better at higher cell doses (30 and 150 X 10(6) cells). Immunization experiments with allogeneic and semiallogeneic erythrocytes or mitomycin- or heat-treated lymphocytes indicated that the antigenicity of the cells was not directly related to the cell surface concentration of antigen and was independent on the proliferative capacity of the lymphocytes; it was, however, curtailed by heat treatment of these cells. The 3 X 10(6), but not the 0.3 or 30 X 10(6) dose of semiallogeneic cells primed efficiently for a secondary hemagglutinin and cytotoxic response. I.v. injected 51Cr-labelled allogeneic and semiallogeneic lymphocytes showed different localized patterns. Between 4 and 24 hr after injection allogeneic lymphocytes were apparently more rapidly lost from the recipient lymph nodes. Collectively, these data indicate that the different immunizing properties of i.v. injected allogeneic and semiallogeneic lymphocytes are not simple consequences of the antigen dose transferred, but suggest that different localization patterns might influence the ability of these cells to induce cytotoxic and hemagglutinating alloantibody formation.

Absorption↗
PubMed1977

A comparison of immune responses against AG-B and non-AG-B antigens, presented alone or together.

By exploiting congenic rat strains (HO.B2 and PVG/c) cell-mediated immune responses against Ag-B antigens alone were measured and compared with responses against (1) non-Ag-B antigens and (2) Ag-B and non-Ag-B antigens in combination. It was confirmed that multiple non-Ag-B antigens provoke prompt first-set skin graft rejections, but are much weaker than Ag-B antigens in stimulating both graft-versus-host (GVH) and cytotoxic activity. No evidence of synergistic interaction was found between anti-Ag-B and anti-non-Ag-B responses either by GVH assay or in the generation of cytotoxic cells. Specific partitioning of cytotoxic cells on antigenic monolayers suggested that cytotoxic cells on antigenic monolayers suggested that cytotoxicity is predominantly directed against Ag-B antigens. The measurements of GVH activity consolidate previous work, which suggested that 4.5 to 12% of nonimmune T cells can respond to each Ag-B determined antigenic complex and eliminate the possibility that most of these cells were responding to non-Ag-B antigens. Two principles for measuring GVH activity were compared: (1) 3H-thymidine incorporation into donor lymphocytes at 24 hr after transfer to irradiated F1 hybrid recipients and (2) the popliteal lymph node assay, which depends on a secondary phase of host cell proliferation.

Animals↗