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Biomedical subjects

L J Knott

Publications and source records attributed to L J Knott.

9 recordsLinked to original sources
PubMed1986

CD2 and CD3 antigens mobilize Ca2+ independently.

Antigen-induced stimulation of T cells is mediated via the CD3 antigen receptor (Ti) complex and monoclonal antibodies (mAb) reacting with CD3 and Ti result in rapid intracellular Ca2+ mobilization, followed by monocyte-dependent proliferation. Combinations of mAb to CD2, the sheep red blood cell receptor, also mobilize calcium and induce mitogenesis and purified phytohemagglutinin (PHA) stimulates T cells predominantly by interaction with this molecule. It has been suggested that activation via CD2 requires the presence of CD3 and that the hydrophobic epsilon chain of CD3 is the T cell calcium channel. To investigate this further we have obtained large numbers of natural killer (NK) cells which express CD2 but not CD3 from a patient with a chronic expansion of this lymphocyte subpopulation. It is shown that calcium mobilization can be induced in these cells by mAb to CD2 and purified PHA but not by anti-CD3 mAb. This indicates that calcium mobilization can be induced via the CD2 molecule in NK cells not expressing CD3 and that activation through CD2 is separate from the antigen receptor CD3 pathway.

Aminoquinolines↗
PubMed1986

T cell receptor gene rearrangements define a monoclonal T cell proliferation in patients with T cell lymphocytosis and cytopenia.

We have used probes from the T cell receptor beta and gamma chain loci to investigate the clonality of T lymphocytes in eight patients with T cell lymphocytosis and cytopenia (TCLC). This syndrome, which is strongly associated with rheumatoid arthritis, is characterized by peripheral blood and bone marrow lymphocytosis and neutropenia, red cell aplasia, or both. By means of T cell monoclonal antibodies and flow cytometry, T lymphocytes from patients with this syndrome have been shown to have characteristic immunologic features. Investigators have disagreed as to whether the syndrome represents a T cell malignancy or a more benign immunologic disorder. DNA from five of five patients with symptomatic "classic" T cell lymphocytosis with cytopenia demonstrated unique rearrangements of the T cell receptor beta chain locus, whereas neither of two patients with atypical features showed rearrangement. In addition, we found evidence for gamma chain rearrangement in those DNAs with clonal beta chain rearrangement. We thus postulate that the classic form of this syndrome is associated with a monoclonal proliferation of T cells. Its potential relationship to T cell chronic lymphocytic leukemia is discussed.

Aged↗
PubMed1985

Bone marrow T cell colony-forming cells: studies of their origin and use in monitoring T cell-depleted bone marrow grafts.

Peripheral blood T cell colony forming cells (T-CFC) are mature T cells. When blood was fractionated into sheep red blood cell receptor positive (E+) and negative (E-) fractions, T cell colony growth was largely restricted to the E+ population. When bone marrow was similarly fractionated, many colonies grew from the E- cells but myeloid colonies also grew making interpretation of colony numbers difficult. We have, therefore, also assessed T cell proliferation during culture as an expansion index (EI) by determining the absolute number of T cells pre and post culture. This data shows that T cell expansion is on average nine times greater in the E- marrow fraction than in the E+ fraction. Studies are presented suggesting that this is because marrow E- cells contain appropriate accessory cells and that high numbers of T cells inhibit T cell growth. The cells giving rise to bone marrow T cell colonies thus appear to be contaminating mature T cells rather than pre-thymic progenitor cells. We have measured T cell expansion in culture as a sensitive assay of T cell contamination following procedures to remove T cells from bone marrow grafts for the prevention of graft versus host disease (GVHD).

Bone Marrow↗
PubMed1984

Unusual T cell proliferations and neutropenia in rheumatoid arthritis: comparison with classical Felty's syndrome.

4 patients are described with rheumatoid arthritis, splenomegaly, neutropenia and an unusual proliferation of T cells in the blood and marrow. These patients are clinically similar to patients with classical Felty's syndrome but can be distinguished from them by staining blood and marrow mononuclear cells with a panel of monoclonal anti-T cell antibodies. The T cells from patients with T cell proliferations stain with UCHT1 (OKT3 equivalent) and UCHT4 (OKT8 equivalent but do not stain with a panel of OKT1-like antibodies. In 7 patients with classical Felty's syndrome there was no increase of UCHT4 cells in the blood and the large majority of T cells stained with OKT1-like antibodies. The marrows from the patients with T cell proliferations contain plentiful haemopoietic progenitor cells and it is probable that the T lymphocytes suppress their normal maturation. There was a poor response to splenectomy in 2 patients with T cell proliferations, and single cytotoxic drug therapy may be more appropriate when therapy is required. The literature is reviewed and it is suggested that the T cell proliferations may be secondary to the rheumatoid process.

Adult↗
PubMed1983

T cell regeneration after allogeneic and autologous bone marrow transplantation.

Venous blood T cell phenotypes were analysed with monoclonal antibodies after 11 allogeneic and 17 autologous bone marrow transplants. In seven cases studied in the early regenerative period, cells with a thymocyte phenotype were present in the blood. In the large majority of patients treated with both allografts and autografts there was an imbalance of phenotypic 'helper' and 'suppressor' T cell subsets with initially a relative and later an absolute increase of 'suppressor' T cells. This imbalance was still present at over 250 d in eight out nine cases. Suppressor T cells bearing HLA-Dr antigens were abundant in one case of fatal GVHD but not in another, and were also increased following two autografts. It is concluded that T cell phenotyping is not of diagnostic value in sick patients following bone marrow transplantation when graft-versus-host disease is suspected.

Adolescent↗
PubMed1982

Bone marrow processing and cryopreservation.

Three different closed procedures for concentrating bone marrow progenitor cells prior to cryopreservation have been compared. These were by a manual double centrifugation method, a Hemonetics 30 cell separator and an Aminco Celltrifuge. The best results were achieved using the paediatric pheresis set on the Hemonetics model 30. Marrow was frozen in 120 ml aliquots in a programmed freezer with rapid cooling of the freezing chamber during the phase change from the liquid to the solid state. After freeze-thawing the average nucleated cell recovery was approximately 50% and the progenitor cell recovery 80%.

Bone Marrow Cells↗
PubMed1982

Studies of circulating hemopoietic progenitor cells in human fetal blood.

High levels of committed erythroid and granulocytic/monocytic progenitor cells have been demonstrated in fresh blood obtained at fetoscopy. The fetal progenitor cells were more sensitive to appropriate stimuli (erythropoietin and colony-stimulating factor) than adult progenitor cells grown under the same conditions, and this was shown to be due to intrinsic differences in the progenitor cells at the different developmental stages.

Adult↗
PubMedDate not supplied

CFU-GM and T cell subsets in young red cell collections.

Young red cells (YRBCs) prepared using cell separators contain large numbers of white cells. The absolute numbers and percentages of different lymphocyte subsets and progenitor cells in YRBC collections were assessed before and after filtration through two white cell filters. It was found that the filters do not take up or selectively allow through any one lymphocyte subset and that the absolute number of T cells and progenitor cells in YRBC collections after filtration is less than that in normal donor blood.

Blood Donors↗