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Biomedical subjects

A R Hayward

Publications and source records attributed to A R Hayward.

At least 91 records · Page 5Linked to original sources
PubMed1984

Culture and phenotype of activated T-cells from patients with type I diabetes mellitus.

Blood T-cells from 28 patients with type I (insulin-dependent) diabetes (IDDM) of variable duration were examined for the Tac antigen by immunofluorescence, and for proliferation in the presence of interleukin 2 (IL 2). The mean percentage of Tac+ cells in patients whose IDDM was of less than 2-yr duration was 6.2% compared with 2% in patients whose IDDM was of 3 or more years' duration, or in healthy controls. The percentage of Tac+ cells in the patients' blood correlated positively with the amount of thymidine uptake in a 24-h culture of blood mononuclear cells and with the percentage of T-cell blasts generated in a 6-day culture. The patients' T-cell blasts stained with OKT 4 or OKT 8, suggesting that each of these subsets is present in the activated T-cell population in the patients' blood. The T-cell blasts did not show specificity for pork insulin in an antigen restimulation assay. There was no correlation between increased Tac+ cells and the presence or absence of islet cell antibodies. If T-cell activation in IDDM occurs as a result of recognition of islet cell antigens, our results suggest that both HLA-DR-restricted (OKT 4+) and A-, B-, and C-restricted (OKT 8+) T-cell subsets contribute.

Adolescent↗
PubMed1984

Human newborn autologous mixed lymphocyte response: frequency and phenotype of responders and xenoantigen specificity.

The response of human newborn lymphocytes in autologous mixed lymphocyte culture was examined for specificity (by restimulation), responder cell phenotype, and responder cell frequency. When the newborn T cells were separated from non-T cells by rosetting with sheep erythrocytes (E) in fetal calf serum (FCS), approximately 1:20,000 T cells proliferated. These responders had specificity for E + FCS, were T4+, and were self-restricted. Significant numbers of responder T cells were not found when newborn T and non-T cells were separated by nylon wool. Responses in parallel autologous cultures of adult T cells showed that 1) adults had a higher frequency than newborns of E + FCS specific responders, 2) evidence for self specificity was lacking in restimulated cultures, and 3) occasional responses to antigen on the surface of monocytes could not be excluded.

Adult↗
PubMed1984

Specific immunity after congenital or neonatal infection with cytomegalovirus or herpes simplex virus.

Infants or children who had congenital or neonatal infection with cytomegalovirus (CMV) or herpes simplex virus (HSV) have fewer than 1:30,000 mononuclear cells in their blood lymphocytes preparations that proliferate in cultures stimulated with the corresponding viral antigens. CMV and HSV responder cell frequencies in children and adults whose immunity followed postnatal infection with these viruses are 1:10,000 to 1:20,000. The low precursor frequency after congenital or neonatal infection is not associated with defective antigen processing by monocytes or nonspecific immunosuppression. Phenotypic changes in T cell subsets and the presence of antibody in the subjects suggests that the virus(es) do indeed elicit an immune response, but that this response is quantitatively deficient.

Adolescent↗
PubMed1984

B cell numbers and responses in patients with common variable immunodeficiency and nodular lymphoid hyperplasia of the bowel.

Nodular lymphoid hyperplasia ( NLH ) of the intestine is a lymphoid proliferation which occurs in patients with common variable immunodeficiency disorders ( CVID ). The nodules contain B cells but their pathogenesis is unknown. To determine whether the presence or absence of NLH might be associated with blood B cell abnormalities we studied CVID patients with and without NLH . CVID patients with NLH had a higher percentage of B cells in their blood than those without NLH . Blood lymphocytes from both groups of CVID patients proliferated less well in Cowan Staph. A stimulated cultures than control lymphocytes. Similar trends were observed in cultures stimulated with pokeweed mitogen and analyzed by karyotype. Our results suggest that blood B cells from patients with NLH are relatively unresponsive to B cell mitogens despite their near-normal numbers.

Adolescent↗
PubMed1983

The human fetus and newborn: development of the immune response.

Maturation of the immune system starts early in fetal life. Lymphocytes of the B series develop in the liver by 9 weeks' gestation and are present in the blood and spleen by 12 weeks. T lymphocytes start to leave the thymus from about 14 weeks' gestation and subsequently cells with helper and suppressor phenotypes are present in the spleen. The relative lack of development of secondary lymphoid tissues in healthy fetuses most probably reflects the lack of antigen stimulus. Newborn plasma contains adult levels of IgG which is acquired across the placenta from the mother. The small amounts of IgM (less than 20 mg/dL) which are normally present in healthy newborns have been reported to include antibody with specificity for maternal lymphocytes. IgA synthesis normally starts in the secretory immune system, about 2-3 weeks after birth. Poor antibody responses by newborns following immunization, especially with bacterial capsular polysaccharides, suggest that newborn immune responses are immature as compared with adults. The susceptibility of newborns to severe HSV and VZV supports this view. In vitro correlates of this immaturity include 1) deficiency of the response by newborn B cells to polyclonal activators, and 2) a lack of T cells which proliferate in HSV- or VZV-stimulated cultures. These characteristics more likely result from a lack of prior antigen stimulation and resulting clonal expansion than from intrinsic lymphocyte suppression. Antigen handling by newborn monocytes, in contrast, appears to be mature by the time of birth.

Antibodies↗
PubMed1982

Probable graft-vs-graft reaction in an infant after exchange transfusion and marrow transplantation.

A newborn with graft-vs-host (GVH) disease following an exchange transfusion was treated by attempting to eradicate the incompatible graft and to reconstitute the child hematologically and immunologically with a bone marrow transplant. The patient was a female term infant (blood group B, Rh+ Coombs test positive) who received a one-unit group O, Rh- exchange transfusion from an unrelated female donor for hyperbilirubinemia due to ABO incompatibility on day 2. Signs of acute GVH disease began on day 8 and the clinical diagnosis was supported by skin biopsy. With antithymocyte globulin and high dose dexamethasone, the GVH reaction improved somewhat. Cyclophosphamide, 200 mg/kg total dose, was given over four days followed by a marrow graft from a brother who was HLA-A, B identical, and probably also D locus compatible in mixed lymphocyte culture. All signs of GVH resolved with cyclophosphamide treatment and hematologic reconstitution was evident by 14 days after transplant. Two weeks later the GVH reaction and aplastic anemia recurred and Y chromatin was detected in only 6% of marrow cells. The infant died on day 80. Autopsy showed disseminated candidiasis, disseminated cytomegalovirus infection, thymic dysplasia, hypoplastic marrow, and other histopathologic changes consistent with GVH disease. The persistence of female cells in blood and bone marrow and the destruction of the reconstituted marrow suggest that the original incompatible transfusion-derived graft was not eliminated and that it ultimately rejected the histocompatible marrow graft.

ABO Blood-Group System↗
PubMed1982

Pre-B cell suppression by thymoma patient lymphocytes.

T lymphocytes from the blood of two thymoma patients with hypogammaglobulinaemia suppressed the in vitro proliferation of allogeneic pre-B cells. Both patients lacked pre-B and B cells in blood and bone marrow. It is possible that pre-B cells, as well as B cells, may be targets for suppression by T cells in thymoma patients with hypogammaglobulinaemia.

Adult↗
PubMed1981

Requirement for OKT8+ suppressor cell proliferation for suppression by human newborn T cells.

The percentage of cells bearing the suppressor phenotype OKT8+increases in PWM-stimulated cultures of human newborn lymphocytes. Prevention of this increase either by adding 50 microM deoxyguanosine to the cultures of by pretreating the newborn cells with OKT8 and complement reduced the suppressor activity of newborn T cells. These results suggest that newborn T cells are not intrinsically suppressive, but that they become so in vitro after stimulation by PWM.

Adenosine↗
PubMed1981

Newborn T cell suppression: early appearance, maintenance in culture, and lack of growth factor suppression.

Human newborn T lymphocytes suppress the responses of adult lymphocytes to several stimuli, including the T dependent differentiation of adult B cells to plasma cells (PC) by pokeweed mitogen (PWM) stimulation. We tested blood from premature babies to show that the suppressor activity for PWM-induced B cell differentiation appeared by 26 weeks' gestation. Cord blood from full term babies delivered by Caesarean section also suppressed PC differentiation showing that maternal labor is not a prerequisite for suppression. Eleven percent of freshly isolated newborn T cells bore the putative suppressor phenotype OKT 8 and 81% had the putative helper phenotype OKT 4, so the increased suppression and diminished help of newborn T cells was not associated with an imbalance of phenotypic helper or suppressor cells. The function of newborn T cells was further investigated by establishing the cells in continuous culture with T cell growth factors. The polyclonal lines obtained suppressed adult PWM-induced PC differentiation and were inefficient helpers so their functional characteristics appear to be maintained in culture without changes in the balance of help and suppression. PHA-stimulated newborn lymphocytes were themselves efficient producers of T cell growth factors. We conclude that newborn T cells can suppress without lectin activation and that the suppressor activity that is found is a stable intrinsic characteristic of the cell.

Animals↗
PubMed1981

Characterization of the T lymphocyte colony-forming cells and evidence for the acquisition of T cell markers in the absence of the thymic microenvironment in man.

The nature of the T colony-forming cell (T-CFC) in agar is still controversial. We present evidence that blood mononuclear cells depleted of T cells by E-rosetting or lysis with OKT 3 and complement can give rise to E+ OKT 3+ colonies in the presence of supernatants of PHA-stimulated lymphocytes (P-SUP) containing a cell growth factor. Both OKT 4+ (67%) and OKT 8+ (32%) cells were found in the colonies, and less than 10% of these cells were Ia+. We consider that colonies in agar can arise from the proliferation and maturation of a circulating immature progenitor (T colony-forming cell, or T-CFC) that does not need the thymic environment to acquire the OKT 3, 4, and 8 antigens or E receptor. In contrast, Ia+ OKT 3+ cells that are maintained by P-SUP in long-term liquid culture are reportedly derived from mature T cells, and this proliferation might represent the counterpart of the in vivo response to any mitogenic stimulation of the peripheral compartment of mature T cells.

Antibodies↗
PubMed1981

Growth of pre-B cells in cultures of bone marrow from children with acute lymphoblastic leukaemia and other diseases.

Pre-B cells from the bone marrow of children with acute lymphoblastic leukaemia (ALL) survived up to 144 hr after the completion of treatment and divided in culture with maximum cell numbers at 24 hr. There was no rise in B cell number and no evidence of differentiation from pre-B to B cells. Binucleated pre-B cells in cultures containing cytochalasin B confirmed that pre-B cell division was occurring. Cycloheximide reduced cell numbers in culture but bromodeoxyuridine did not. Pre-B cell numbers also increased in culture of morphologically normal marrows from treated and untreated patients with solid tumours, and probably in normal marrows from patients with non-malignant diseases.

Adolescent↗
PubMed1981

Increase and inhibition of pre-B cell proliferation in culture, by T cells.

T cells may either increase or decrease in vitro proliferation of marrow pre-B cells from patients with acute lymphatic leukaemia after withdrawal of successful treatment. There is less proliferation when T cells are removed by E rosetting, and repletion of T cells restores proliferation. When additional T cells from the patients were added to the patients' marrows, proliferation was increased more effectively than with T cells from healthy subjects; there was no evidence of an allogeneic effect. In contrast, normal T cells stimulated with concanavalin A suppress proliferation. There was no evidence of differentiation into B cells.

Adolescent↗