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Results for “Lymphocyte Transfusion”

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At least 181 records · Page 10Linked to original sources
PubMed1982

Nonspecific suppression of anti-graft immunity by antigen-specific T suppressor cells.

The specificity of T suppressor cells induced by intravenous administration of irradiated allogeneic spleen cells was studied in mice by means of a delayed type hypersensitivity (DTH) assay. T suppressor cells induced by either H-2K, H-2I or H-2D incompatible cells were found to be specific for the inducing alloantigen. Such antigen specific T suppressor cells can suppress the response to another H-2 alloantigen, provided it is administered together with the alloantigen that had induced the T suppressor cells. Similarly, T suppressor cells induced by non-H-2 alloantigens can suppress the response to H-2 alloantigens if administered simultaneously.

Animals↗
PubMed1975

Immunotherapy of malignant disease in man.

At present active specific immunotherapy should only be attempted where a tumour is shown to be antigenic and immunogenic, patients are immunocompetent, large numbers of tumour cells can be stored and minimal residual disease can be achieved without heavy immunosuppression. Acute myeloblastic leukaema (AML) satisfies such criteria reasonable well and evidence is presented that treatment with BCG and irradiated allogeneic AML cells is of value in this disease. It is suggested that there is insufficient evidence at present to justify embarking on similar regimes in most of the malignant lymphomas.

Animals↗
PubMed1994

Detection of cochlear dysfunction by the measurement of transiently evoked otoacoustic emissions in guinea pigs with autoimmune-induced labyrinthitis.

For the evaluation of functional inner ear lesions caused by an autoimmune-induced labyrinthitis, transiently evoked otoacoustic emissions (TEOAEs) were detected in guinea pigs before and after transfer of sensitized lymphocytes from animals suffering from a labyrinthitis induced by the foreign protein keyhole limpet hemocyanin (KLH). Initially TEOAEs were detectable from 47 of 62 ears (76%) in healthy guinea pigs. These animals then were used as recipients for sensitized lymphocytes from donors exclusively. Three months after cell transfer the incidence of TEOAEs was reduced to 48% in animals receiving lymphocytes from donors sensitized with KLH intradermally and intracochlearly. In recipients of lymphocytes from donors sensitized only intradermally and in untreated animals no significant alteration of the TEOAE incidence was found. These findings showed strong correlation with those from scanning electron microscopy of the organ of Corti, indicating that the measurement of TEOAE is a useful, time-saving tool for the detection of cochlear dysfunction caused by sensitized lymphocytes in experimental animal. The present findings also show that the migration of sensitized lymphocytes actually leads to functional lesions in the cochlea.

Animals↗
PubMed1983

The role of allogeneic cells in the stimulation of cell-mediated cytotoxicity to leukaemia cells. A family study.

Allogeneic lymphocytes can stimulate cell-mediated cytotoxicity (CMC) in lymphocytes from leukaemia patients against autologous leukaemia target cells. We have compared the capacity of different allogeneic lymphoid cells to stimulate CMC to fresh (i.e., patient) and cultured (MOLT 4, K562) leukaemic target cells in lymphocytes from an acute leukaemic patient and his HLA-identical siblings. Allogeneic lymphoid cells, and particularly a lymphoblastoid cell line, were effective in stimulating CMC to leukaemia targets. In some instances, however, leukaemia cells derived from the patient, mixed with allogeneic lymphoid cells stimulated synergistic CMC to the patient's leukaemia. We also found that the patient's leukaemia cells alone were able to stimulate CMC in HLA-identical sib lymphocytes to fresh and cultured leukaemia targets. Extra specificities on fresh leukaemia cells were revealed when these cells induced unpredicted CMC on normal lymphocyte targets when added to mixed lymphocyte cultures (MLC) between related and unrelated lymphocytes. Cytotoxic lymphocytes generated in MLC against the patient's HLA antigens were absorbed by monolayers of lymphocytes and leukaemia cells of the same HLA type as the patient, leaving residual CMC to fresh (patient) and cultured (K562) leukaemia target cells. In addition, CMC to the patient's leukaemia cells, stimulated in lymphocytes from the patient's HLA-identical sib by allogeneic cells, was absorbed by a monolayer of these allogeneic cells. This suggests cross reactivity between determinants on the leukaemia and allogeneic lymphocytes. The results of this study are consistent with expression of 'leukaemia antigen', which are not restricted to leukaemia cells but may also be expressed on lymphocytes.

Aged↗
PubMed1983

Antibody-dependent cellular cytotoxicity-mediated serotherapy against murine neuroblastoma. II. In vitro and in vivo treatment using effector cells from normal and X-irradiated humans.

Human peripheral lymphocytes (HLc) have been studied in vitro as possible effector cells in an antibody-dependent cellular cytotoxicity (ADCC) reaction. HLc were found to be active against murine neuroblastoma cells (MNB) inoculated into the flank of syngeneic mice. Both the time of onset of tumor appearance and the mean survival time of tumor-bearing host mice were beneficially influenced. Occasional animals could be cured of up to 10(5) tumor cells (1--10 cells of MNB are lethal). This level of tumor cytotoxicity approaches that of tolerance-dose chemotherapy and is without demonstrable side-effects. HLc from patients who had just received = 3,000 rads fractionated therapeutic X-irradiation were equally effective as HLc from control non-irradiated donors when assayed at equivalent HLc : tumor cell ratios. HLc could also inhibit MNB tumor cell growth in the ascitic form, confirming in vivo activity. Overall, HLc appeared almost as active as rat spleen cells in mediating a useful anti-tumor ADCC. This approach may ultimately prove useful in man, especially in the peritoneal cavity, and is currently limited only by the need to develop appropriate antisera. It is proposed and emphasized that such antisera need not necessarily be directed at tumor-specific antigens. Organ-specific antibodies such are already known to develop spontaneously in some human auto-immune diseases might be equally useful and are a naturally occurring potential source of appropriately expressed genetic material.

Animals↗
PubMed1988

Clinical adoptive chemoimmunotherapy with allogeneic alloactivated HLA-haploidentical lymphocytes: controlled induction of graft-versus-host-reactions.

A total of 13 cancer patients were treated with Adoptive Chemoimmunotherapy (ACIT) using alloactivated HLA haploidentical lymphocytes. Donor lymphocytes were activated in vitro using a pool of irradiated allogeneic lymphocytes (MLC-cells) and some further expanded by culturing in T-cell growth factor (TCGF-cells). The first 6 patients received i.v. cyclophosphamide (CPM) followed 24 h later by escalating doses of MLC-cells, then 7 days later they received an infusion of TCGF-cells. Minimal toxicity was seen. The next 7 patients received CPM (800 mg/m2) and a combined MLC and TCGF-cell infusion (total cell dose ranged from 0.79 x 10(10) to 2.26 x 10(10)). Of these 7 patients, 3 developed mild graft-versus-host reaction (GVHR) which resolved without treatment, and 2 patients had progressive GVHR which was arrested by methylprednisolone (2 mg/kg). Peripheral blood lymphocytes from these 2 patients, during the GVHR, had increased activated T-cells (OKT-10+ and OK-Ia+). In vitro expansion, in TCGF, of these activated T-cells enabled HLA typing to prove they were of donor origin. Only 1 clinical antitumor response was observed in the first 6 patients. The results of this study indicate that this form of ACIT can be given to patients with acceptable toxicity. Self-limited or easily controlled GVHR may be induced and primed donor cells persisting in the circulation are probably responsible. Further testing is required to determine whether the immune response induced by this form of ACIT may be therapeutically effective.

Child↗
PubMed1989

Failure of specific adoptive immunotherapy owing to survival and outgrowth of variant cells.

Adoptive immunotherapy, the transfer of spleen cells from immunized mice to mice with a small tumor, was usually curative for mice with the P815 mastocytoma provided that steps were taken to prevent the generation of tumor-induced suppressor cells in the recipient animal. However, failure of adoptive immunotherapy of the P815 tumor, resulting in regrowth of either the primary intradermal or a metastatic tumor, was observed in 10 out of 112 animals receiving graded doses of 7.5 x 10(7) to 3.0 x 10(8) immune spleen cells. Examination of the ten tumors in mice that failed to respond to therapy revealed that seven of them were significantly less susceptible than the original P815 tumor to rejection in vivo by transferred anti-P815-specific effector cells. In addition, nine of the ten therapy-failure tumors were also less susceptible than the original P815 tumor to lysis in vitro by P815-specific, but not DBA/2-specific, cytotoxic T lymphocytes. Sensitivity to lysis by tumor-specific cytotoxic T cells was not, however, strongly correlated with sensitivity to rejection in vivo by P815-specific effector spleen cells. Neither in vivo sensitivity to rejection, nor sensitivity to cytotoxic T cells, was correlated with alterations in class I major histocompatibility complex antigen expression. These results suggest that the survival and outgrowth of variant tumor cells was frequently the cause of failure of specific adoptive immunotherapy of the P815 tumor, and that selection for cells with a reduced sensitivity to killing by cytotoxic T cells was only one mechanism that might lead to an immunotherapeutic failure.

Animals↗
PubMed1989

In vivo and in vitro synergistic antitumor effect of interleukin-2-cultured tumor-bearer spleen cells and immune fresh spleen cells.

The synergistic antitumor effect of interleukin-2(IL-2)-cultured tumor-bearer spleen cells (cultured lymphocytes) and immune fresh spleen cells was examined. Tumor-bearer cultured lymphocytes were obtained by culturing BALB/c spleen cells from syngeneic MOPC104E-tumor-bearing mice for 11 days with crude IL-2 and a soluble tumor extract. These cultured lymphocytes had weak antitumor activity when transferred i.p. into tumor-bearing mice that had been inoculated i.p. with 10(5) tumor cells 5 days previously. Immune fresh spleen cells, obtained from mice in complete remission after the treatment with cyclophosphamide, also had weak antitumor activity when transferred at the same schedule. The cultured cells and the fresh cells, mixed together before transfer, significantly augmented the therapeutic effect. At least 1 x 10(7) tumor-bearer cultured lymphocytes and 4 x 10(7) immune cells were needed for the synergistic effect. A tumor-specific combination was needed for both cultured and fresh cells. The effective subpopulation of tumor-bearer cultured lymphocytes was a cytotoxic one from an Lyt2+ precursor, and that of the immune fresh spleen cells was noncytotoxic, Lyt1+ and Lyt2+ T-cells. A similar synergistic effect was also observed during in vitro coculture of tumor-bearer and immune cells. Cytotoxicity, as assessed by the 51Cr-release test, of tumor-bearer IL-2-cultured lymphocytes was maintained most effectively after 3 or 4 days of culture without IL-2 when the lymphocytes were cocultured with immune fresh spleen cells and tumor cells.

Animals↗