Spectrum of ultraviolet radiation on human B and T lymphocyte viability.
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Biomedical subjects
Publications and source records attributed to R Hong.
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Thymic fragments were maintained in organ culture until egress or deterioration of the leucocyte component was near completion. These depopulated cultured thymic fragments were then implanted into immunologically competent mouse recipients. Acute immunologic rejection was not observed in mice given cultured thymic allografts. If the organ culture period was approximately 2 weeks, lymphoid repopulation and newly developed Hassall's corpuscles were observed 7-10 weeks after implantation. If the initial culture period was extended to 3 weeks, transplanted fragments developed as unusual repopulation pattern, characterized by eosinophils, macrophages and plasma cells. This finding could be interpreted as a protracted allograft rejection or, more likely, a loss of ability of the thymic epithelium to attract or differentiate the types of precursors usually attracted to the normal gland. When cultured and non-cultured tissues were simultaneously transplanted in a single recipient, the non-cultured tissue was acutely rejected and became fibrous, while the cultured thymus assumed the appearance of a normal lymphoid organ without any neighbouring inflammatory reaction.
A child with a poorly differentiated lymphoma developed varicella while being treated with maintenance chemotherapeutic agents. He received a transfusion of nonirradiated leukocytes from 1 unit of whole blood donated by a healthy volunteer who had recently recovered from varicella. The clinical course of varicella was aborted, but a classic graft-versus-host reaction developed and ultimately proved fatal. The host may have presented a large population of antigen-bearing cells to an infusion of presensitized immunocompetent donor cells, leading to an overwhelming aggressor lymphocyte reaction. We speculate that a modified approach using irradiated donor cells could be of benefit in the treatment of varicella infections in the immunosuppressed host.
A 6-month-old girl with congenital thymic dysplasia or Nezelof's syndrome (lack of T cell function and normal levels of immunoglobulins) was given a transplant of a human thymus gland from a 14-week-old fetus and is surviving 36 months after transplant. Her clinical condition is the principal index of the success of the transplant since most in vitro and in vivo data indicate a full immunologic restoration has not been achieved. However, the number of E-rosettes in the peripheral blood has increased, the number of surface immunoglobulin-bearing cells has decreased, but there is little improvement in mitogen responsitivity. Immunoglobulin levels have increased with age, but there is no demonstrable specific antibody activity. Nevertheless, she remains free of infection, living in an unprotected environment.
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Circulating thymic-hormone activity was assayed by measuring Thy 1-2 antigen induction on null lymphocytes from athymic mice incubated with human plasma or serum. Plasma from 19 normal children aged under 10 had inductive activity equivalent to 10-6-16-2 ng thymopoitin/ml. Plasma from 15 infants were severe combined immuno-deficiency, 2 of whom had appreciable immunoglobulin synthesis, and from 2 infants with DiGeorge syndrome had little or no inductive activity. Successful reconstitution with thymus or bone-marrow grafts and with red-cell infusions (if adenosine-deaminase deficiency is present) was followed by a rise in circulating thymic-hormone activity.
Patients with systemic lupus erythematosus lacked suppressor T cell function. Suppressor cell activity was induced in cells from many of these patients by incubation with thymosin or cultured thymic epithelium. These results suggest that thymic manipulation may be a useful therapeutic modality in this disease.
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Thymocytes and macrophages can be involved in the generation and perpetuation of autoimmune disorders in many ways. Evidence continues to mount for their active role. Although a significant association seems likely, one should remember that B cells and complement-directed granulocyte destruction may be equally if not more important. Furthermore, a combination of processes is not precluded by any fundamental biological law. Appropriate and effective therapy requires acceptance of this concept and further studies should attempt to define the interrelationships of these processes and focus upon methodology to determine their relative roles in a given situation.
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A double antibody method for quantitation of urinary immunoglobulins that is sensitive enough to avoid the need for urine concentrations has been developed. The first antibody is goat antiserum monospecific for the heavy chains of IgA, IgG, and IgM. The second, and precipitating, antibody is developed in rabbits made tolerant to human IgG. Normal values for male and female children and adults are presented. Elevated levels of urinary IgA and IgG were found after urinary tract infection.
A patient with severe combined immunodeficiency has been given a transplant of thymic epithelium obtained from short-term culture of normal human thymus. 4 wk after transplantation immunoglobulin was detected and the patient now has normal levels of the three main classes. Functional antibodies of four specificities have been detected. An increase in reactivity to allogeneic cells and phytohaemagglutinin has been observed, with an increase in E rosettes; a positive delayed skin test to candida antigen is now present. The patient has shown reversal of wasting and has been free of infection for 7 months since receiving the transplant. It appears that under certain circumstances thymic epithelium reconstitutes both T and B cell functions.
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An infant with severe combined immunodeficiency had normal numbers of lymphocytes which bore E rosette and surface Ig markers in an appropriate distribution. However, only minimal responsivity to in vitro stimulation by mitogens and allogenic cells, and none to antigens could be elicited; functional antibody responses were also nil, except to cytomegalovirus. Intrauterine-acquired cytomegalovirus may have caused his immune dysfunction, although the possibility of a postnatal infection cannot be excluded. Therapy with transfer factor and thymus transplantation was unsucessful in restoring immunity and may have aggravated a pre-existing monoclonal gammopathy. It is possible that the monoclonal protein was derived from B-cells transplacentally received from the patients mother.
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