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M S Tsoi

Publications and source records attributed to M S Tsoi.

34 records · Page 2Linked to original sources
PubMed1981

Specific suppressor cells and immune response to host antigens in long-term human allogeneic marrow recipients: implications for the mechanisms of graft-host tolerance and chronic graft-versus-host disease.

After marrow grafting from HLA-identical siblings, anti-host immune reactivity and suppressor activity were examined in long-term patients with and without C-GVHD. Lymphocytes (of donor origin) from 17 of 32 patients with C-GVHD showed MLR to non-HLA antigens of stored host lymphocytes, and lymphocytes from 8 of 21 patients with C-GVHD exhibited cytotoxicity to host skin fibroblasts. Lymphocytes from only 2 of 15 patients without C-GVHD, however, showed significant MLR to host lymphocytes and none of 16 had cytotoxicity to host fibroblasts. Suppressor activities differed in the two patient groups. Patients without C-GVHD had circulating suppressor cells that specifically inhibited donor MLR to TNP-host lymphocytes but not to TNP-donor, TNP-unrelated and unmodified unrelated lymphocytes. On the other hand, patients with C-GVHD had predominantly suppressor cells that inhibited donor MLR to TNP-unrelated and unmodified unrelated lymphocytes. These findings indicate that anti-host immune reactivity in the absence of specific suppressor cells plays a role in C-GVHD, and that graft-host tolerance in the stable chimeras may be maintained by specific suppressor cells.

Acute Disease↗
PubMed1980

Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients.

This study of chronic graft-versus-host disease (GVHD) describes the clinical, pathologic and laboratory features, and the causes of morbidity and mortality in 20 patients who received allogeneic marrow transplants from HLA identical sibling donors. Chronic GVHD is a pleiotrophic syndrome with variability in the time of onset, organ systems involved and rate of progression. The clinical-pathologic features resemble an overlap of several collagen vascular diseases with frequent involvement of the skin, liver, eyes, mouth, upper respiratory tract, esophagus and less frequent involvement of the serosal surfaces, lower gastrointestinal tract and skeletal muscles. Major causes of morbidity are scleroderma with contractures and ulceration, dry eyes and mouth, pulmonary insufficiency and wasting. Chronic GVHD has features of immune dysregulation with elevated levels of eosinophils, circulating autoantibodies, hypergammaglobulinemia and plasmacytosis of viscera and lymph nodes. In this study, three patients had limited chronic GVHD with relatively favorable prognosis characterized by localized skin involvement and/or hepatic disease without chronic aggressive histology. Most patients, however, had extensive disease with a progressive course. Survival was largely determined by the presence or absence of serious recurrent bacterial infections. The over-all severity of disease was best assessed by using the Karnofsky performance rating.

Adolescent↗
PubMed1980

Cell-mediated immunity to non-HLA antigens of the host by donor lymphocytes in patients with chronic graft-vs-host disease.

Forty-four patients with aplastic anemia or leukemia were given marrow grafts from siblings selected on the basis of HLA-A and -B identity and mutual nonreactivity of their lymphocytes in mixed leukocyte culture (MLC). Twenty-two to 1089 days after grafting, their lymphocytes (of donor origin) were tested for reactivity in MLC to lymphocytes from the host (cryopreserved before grafting), the marrow donor, and unrelated individuals. Lymphocytes from 14 of 22 long-term survivors with chronic graft-vs-host disease (GVHD) showed unidirectional reactivity in response to host lymphocytes manifested as high stimulation indices (SI) and high relative responses (RR). Lymphocytes from only 1 of 12 long-term survivors without chronic GVHD showed unidirectional reactivity to host lymphocytes. Statistical analysis showed that lymphocytes from patients with chronic GVHD displayed anti-host responses that were significantly higher than those of lymphocytes from either marrow donors (p < 0.001) or patients without GVHD (p = 0.03). Lymphocytes from 5 patients with and 5 without acute GVHD, tested shortly after marrow grafting, failed to show responses to host cells. The results are consistent with a participation of cell-mediated immunity of graft against host in chronic GVHD.

Bone Marrow↗
PubMed1979

Nonspecific suppressor cells in patients with chronic graft-vs-host disease after marrow grafting.

Forty-four human long-term survivors after marrow transplantation for aplastic anemia or hematologic malignancy were studied for the presence of circulating nonspecific suppressor cells. Twenty-two of the patients were healthy and 22 had mild to moderately severe chronic graft-vs-host disease (GVHD). Patient mononuclear cells (of donor origin) were tested for their ability to suppress the responses of lymphocytes obtained from the respective marrow donors to alloantigens in mixed leukocyte culture (MLC) and/or to concanavalin A (Con A). Tests were carried out between 199 and 2393 (median 376) days after transplantation. Cells from only 1 of 22 patients without chronic GVHD showed suppression of donor cell blastogeneis responses. In contrast, cells from 11 of 22 patients with chronic GVHD showed more than 30% suppression of donor cell responses in MLC and/or to Con A. The finding of suppressor cells was not related to the time of testing after grafting nor to immmunosuppressive therapy. Nonspecific suppressor activity was abrogated by irradiation with 1600 rads in vitro in five of six cases tested. Nonspecific suppressor cells may be one explanation for the severe combined immunodeficiency and the recurrent infectious complications characteristic of patients with chronic GVHD.

Bone Marrow Transplantation↗
PubMed1978

Deposition of IgM and complement at the dermoepidermal junction in acute and chronic cutaneous graft-vs-host disease in man.

The presence of cutaneous immunoglobulin and complement was investigated in 88 patients with and without graft-vs-host disease (GVHD) after transplantation of bone marrow from HLA identical siblings for the treatment of acute leukemia or aplastic anemia. For comparison, skin biopsies from the patients obtained before transplantation, from 58 healthy individuals (mostly marrow donors) and from four syngeneic marrow recipients were studied. A direct immunfluorescent staining technique was used. Dermo-epidermal IgM deposits were found in 11% of healthy individuals and patients before grafting but were present in 86% of patients with chronic and 39% of patients with acute GVHD. Patients with allogeneic grafts who never had GVHD or who had recovered from it and patients with syngeneic grafts showed findings not different from those in healthy individuals. Findings similar to those with IgM, although less striking, were made for C3, i.e., patients who had chronic or acute GVHD had a high incidence and intensity of C3 deposits at the dermo-epidermal junction. This observation raises the possibility that humoral immunity is involved in the development of GVHD.

Acute Disease↗
PubMed1977

Studies on cellular inhibition and serum-blocking factors in 28 human patients given marrow grafts from HLA identical siblings.

Fifteen patients with aplastic anemia and 13 with acute leukemia were studied 36 to 1547 days after treatment with high-dose cyclophosphamide and/or total-body irradiation and marrow transplantation from HLA identical siblings. Peripheral blood lymphocytes from patients and normals (marrow donors and healthy unrelated individuals) were tested for cell inhibition (CI) of cultured skin fibroblasts from both patients and donors by using the microcytotoxicity assay. In addition, blocking of CI by factors in patient serum was studied. Three groups of patients were studied. Patients in group I were stable long-term survivors without evidence of graft-vs-host diseases (GVHD) between 250 to 1547 days postgrafting. Patients in group II were short-term survivors with or without acute GVHD between 36 and 144 days postgrafting. Patients in group III had chronic GVHD either at the time of testing or developed chronic GVHD subsequent to CI testing between days 61 and 960 postgrafting. Eleven of 14 patients in group I showed absence of both CI and serum blocking and three showed CI and blocking. Patients in group II without acute GVHD showed absence of CI and serum blocking on three occasions, presence of CI and blocking on four occasions, and CI without blocking on three occasions. Patients in group II with acute GVHD showed absence of CI on one occasion and presence of CI and blocking on three occasions. Patients in group III showed absence of CI and blocking on seven occasions and CI without blocking on two occasions. These results suggest that the maintenance of stable graft-host tolerance in long-term survivors after marrow grafting from HLA identical donors does not depend on the presence of serum-blocking factors. Short-term survivors with and without GVHD showed a spectrum of in vitro reactivity with 50% of the patients showing serum-blocking factors, and these results did not appear to be correlated with presence or absence of acute GVHD. Finally, results of the microcytotoxicity assays failed to provide insight into the mechanism of chronic GVHD.

Adolescent↗
PubMed1976

Infusion of donor lymphocytes into stable canine radiation chimeras: implications for mechanism of transplantation tolerance.

Canine radiation chimeras were used to investigate further mechanism(s) responsible for maintaining the stable chimeric state. Chimeras were studied 7 to 46 months after 1200 R total body irradiation and transplantation of marrow from a littermate donor matched at the major histocompatibility complex. An attempt was made to perturb the stable chimeric state by infusion of large numbers (0.6 to 13.7 x 10(8)/kg) of donor peripheral blood lymphocytes into each respective chimera. Two groups were studied: donors in Group A were normal; donors in Group B had been specifically sensitized against minor histocompatibility antigens of the chimera by repeated skin grafts. None of the nine chimeras in Group A developed significant clinical or histologic evidence of graft-vs-host disease (GVHD) after donor lymphocyte infusion. Eight of the 12 chimeras in Group B, however, developed GVHD which was transient in three and fatal in five. The results in Group A are not consistent with classical theories of tolerance, i.e., elimination or inactivation of potentially reactive cell clones, but suggest the presence of an active mechanism suppressing recognition of host antigens by the infused donor lymphocytes and development of GVHD. The results in Group B indicate that this mechanism can be overcome by infusion of sensitized donor cells. In an attempt to elucidate the nature of this postulated active mechanism, the cytotoxicity of donor lymphocytes for fibroblasts of the chimera and the presence or absence of serum-blocking factors were assessed in vitro by using a cellular inhibition (CI) assay. The presence of serum-blocking factors did not protect against the development of significant GVHD in two chimeras (fatal in one). GVHD did not occur in four other chimeras after infusion of cytotoxic donor lymphocytes despite the absence of serum-blocking factors. These and previous results suggest that serum-blocking factors are not the mechanisms suppressing the development of GVHD in canine radiation chimeras, and raise the possibility that a suppressor cell population may be responsible for preventing GVHD.

Animals↗
PubMed1975

Canine marrow transplantation: are serum blocking factors necessary to maintain the stable chimeric state?

Nine long-term canine radiation chimeras and their canine histocompatibility locus (DL-A) compatible, mixed leukocyte culture negative littermate marrow donors were studied between 545 and 1282 days after 1,200 R total body irradiation and marrow grafting. Before the time of testing, marrow donors were immunized against their chimeras by repeated skin grafts which they rejected. Skin fibroblasts from chimeras and their donors were tested for cell inhibition (CI) in the microcytotoxicity assay be exposure to lymphocytes from chimeras, donors and normal dogs and the effects of various sera on CI were evaluated. Lymphocytes from sensitized marrow donors consistently inhibited fibroblasts from the chimeras (eight of nine dogs); CI was abrogated by chimeric serum in only three of eight cases. Only two chimeras showed consistent CI of their "own" fibroblasts; CI was blocked by chimeric serum in one of the two. The remaining seven chimeras did not show consistent CI. Sequential studies in 16 additional recipients of DL-A compatible littermate marrow were carried out from 45 to 439 days after marrow grafting. Seven of the 16 did not show CI of chimeric fibroblasts by chimeric lymphocytes at any time. Nine showed CI on one or several occasions. Serum blocking factors were seen on one occasion in each of two chimeras. In conclusion, the CI assay is able to detect immunity against "minor" histocompatibility systems in dogs. Both long- and short-term chimeras occasionally demonstrated CI of chimeric fibroblasts but serum blocking factors did not appear to be necessary for maintaining stable graft-host "tolerance."

Animals↗
PubMed1975

Marrow origin of canine alveolar macrophages.

Pulmonary macrophages were obtained from a canine radiation chimera 221 days after irradiation. A variant of soluble glutamic oxaloacetic transaminase was utilized to demonstrate that these cells were of donor origin, providing evidence that pulmonary macrophages in the dog are of marrow origin.

Animals↗