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M Theobald

Publications and source records attributed to M Theobald.

7 recordsLinked to original sources
PubMed1992

Host-specific interleukin-2-secreting donor T-cell precursors as predictors of acute graft-versus-host disease in bone marrow transplantation between HLA-identical siblings.

BACKGROUND: Acute graft-versus-host disease (GVHD) is a serious complication of allogeneic bone marrow transplantation from an HLA-identical sibling. There is no practical test before transplantation that gives sufficient information to predict the degree of allogeneic reactivity between HLA-identical siblings. METHODS: We determined the frequency with which host-specific interleukin-2-secreting donor T-cell precursors occurred in 16 consecutive pairs of HLA-identical siblings before they underwent marrow grafting. The results were correlated with the development of acute GVHD after transplantation. RESULTS: High frequencies of host-specific T-cell precursors (> or = 1 per 100,000) were detectable before transplantation in eight donors whose siblings later had severe (grade II or III) acute GVHD. Among the donors to eight patients with mild (grade 0 or 1) acute GVHD, low frequencies (< 1 per 100,000) were found. CONCLUSIONS: Analysis of the frequency of such cells before transplantation may be a useful predictor of severe acute GVHD in allogeneic bone marrow transplantation between HLA-identical siblings. It is possible that the patients at risk for serious acute GVHD after marrow grafting may benefit from some alternative form of immunosuppressive therapy.

Acute Disease↗
PubMed1990

Comparative analysis of in vivo T cell depletion with radiotherapy, combination chemotherapy, and the monoclonal antibody Campath-1G, using limiting dilution methodology.

We have investigated the efficacy of standard conditioning regimens for bone marrow transplantation in depleting functional T lymphocytes in vivo and have compared it with the efficacy of the monoclonal antibody Campath-1G. Using limiting dilution techniques the frequencies of proliferating T cell precursors (PTL), cytotoxic T cell precursors (CTL-p), helper T cell precursors (HTL-p), and mature helper T cells (HTL) were determined before and after treatment. Both total body irradiation and combination chemotherapy with busulfan/cyclophosphamide were highly efficient at depleting PTL, CTL-p, and HTL-p (0-4 days) but spared HTL to a variable extent (0-99.5%). In the majority of patients treated with Campath-1G a similar degree of PTL, CTL-p, and HTL-p depletion was achieved, and, in addition, HTL were effectively removed (greater than 95.5%). These results suggest that Campath-1G could be successfully employed in depleting radio- and chemotherapy-resistant host T lymphocytes prior to T-depleted bone marrow transplantation.

Antibodies, Monoclonal↗
PubMed1990

Frequency, specificity, and phenotype of clonally growing human alloreactive interleukin-2-secreting helper T lymphocyte precursors.

Limiting dilution cultures were performed to detect allospecific IL-2-secreting helper T lymphocyte precursors (HTL-p) among human peripheral blood mononuclear cells, E-rosette-purified (E+) and cell-sorter-separated CD4+/8- as well as CD4-/8+ T cell subsets. Split-well cultures were set up prior to restimulation to assess the antigen specificity of the response. Frequencies of alloreactive IL-2-secreting HTL-p in fully HLA-mismatched responder/stimulator cell combinations ranged from 1/200 to 1/900 (among PBMNC), from 1/50 to 1/301 (among E+ T cells), from 1/36 to 1/220 (among CD4+ T cells), and from 1/38 to 1/450 (among CD8+ T cells). Allospecificity of effector T cells was demonstrated by a strong decline of frequencies obtained after restimulation against unrelated third-party antigens. In clonal segregation analysis, the vast majority of IL-2-secreting progeny (80-90%) were exclusively specific for the original stimulating alloantigen. Finally, the allele specificity of human alloreactive HTL-p was revealed by comparing frequency estimates obtained after restimulation with partially identical stimulator/third-party antigen combinations.

Alleles↗
PubMed1989

Assessment of human allospecific IL-2-secreting helper T lymphocytes in limiting dilution cultures using restimulation and split well analysis.

A limiting dilution (LD) culture was established which allows the detection of allospecific interleukin-2 (IL-2)-secreting helper T lymphocyte precursors (HTL-p) among human peripheral blood mononuclear cells (PBMNC). HTL-p stimulated with allogeneic Epstein-Barr virus-transformed B lymphoblastoid cell lines (EBV-LCL) in the presence of exogenous recombinant IL-2 (r-IL-2) clonally developed into IL-2 secreting effector cells when restimulated against the original stimulating alloantigen. Split well cultures were performed prior to restimulation to assess the antigen specificity of the response. Frequencies of alloreactive IL-2-secreting HTL-p ranged from 1/100 to 1/800. Allospecificity of effector T cells was determined by a strong decline of frequencies obtained after restimulation against third-party antigens. In (clonal) segregation analyses the vast majority of IL-2-secreting progenies (80%) were specific for the original stimulating alloantigen. Allele specificity was disclosed by using class II MHC related third-party restimulator cells. By comparison with LD short-term cultures it became evident that exogenous r-IL-2 in the initial culture period was required to reveal optimal precursor frequencies of IL-2-producing T cells. Furthermore, successful antigenic restimulation was strictly confined to these culture conditions.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Human chorionic gonadotropin levels in various compartments in disturbed early pregnancy.

The hCG level in the uterine cavity was higher than in peripheral blood in a case of choriocarcinoma and in patients with spontaneous expulsion of the conceptus. In two patients with missed abortion, the hCG concentrations in peripheral blood and in serum from the uterine cavity did not differ. In contrast, the hCG concentrations in PF in these patients were lower than in peripheral blood. The measurement of hCG in these compartments may provide evidence concerning the location of the trophoblast.

Biomarkers, Tumor↗
PubMedDate not supplied

A case for autonomy.

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Nursing↗