T-cell Rosettes Research Articles

Immunosuppression following radiation therapy for carcinoma of the nasopharynx.

IMMUNOSUPPRESSION FOLLOWING RADIATION THERAPY FOR CARCINOMA OF THE NASOPHARYNXWILLIAM M. WARA, M.D., THEODORE L. PHILLIPS, M.D., DIANE W. WARA, M.D., ARTHUR J. AMMANN, M.D. and VERNON SMITH, M.Sc.Audio Available | Share

Thymosin activity in patients with cellular immunodeficiency.

An extract of calf thymus, thymosin, induces an increase in percentage of T-cell rosettes when incubated in vitro with sheep erythrocytes and lymphocytes from patients with primary immunodeficiency diseases or viral illness. Precursor lymphocytes are required for this increase to occur. The percentage of T-cell rosettes, when they are normal, is not increased further upon incubation with thymosin. A patient with thymic hypoplasia and immunoglobulin synthesis was selected to receive thymosin in vivo when her T-cell rosettes had increased from 15 to 48 per cent after in vitro incubation with thymosin. During therapy, she clinically improved, the percentage of T-cell rosettes gradually increased to normal, and positive delayed hypersensitivity skin tests developed. Thymosin may be useful clinically for partial reconstitution of cellular immunity. An increased percentage of T-cell rosettes after incubation with thymosin in vitro may predict which patients will respond to thymosin therapy in vivo.

DISSOCIATED LYMPHOCYTE FUNCTION IN NEWBORN INFANTS

The correlation between phytohemagglutin in (PHA) induced blast cell transformation (BCT) and production of lymphotoxin (LT), a cytotoxic mediator of cellular immunity, was studied in the cord blood lymphocytes of 17 normal newborns. Twelve normal adults served as controls. BCT was estimated as uptake of 3-H-thymidine, and LT as the percent inhibition of DNA synthesis of growing target cells. BCT by newborn lymphocytes was slightly greater than that of adults. By contrast, LT production by the newborns was only 40 that of the adults. Calculation of an “LT Index” (ratio of LT production to BCT) revealed that for any degree of BCT, newborn lymphocytes produced only one-fourth as much LT as did adult cells. In 6 infants, the percent of lymphocytes forming rosettes with sheep red cells (T-cell rosettes) averaged 80% (range 63-90%), which is comparable to that of adults. The combination of impaired mediator production with normal BCT represents a dissociation of lymphocyte function which appears to be a stage in the normal maturation of cellular immune competence. This may, in part, explain the undue susceptibility of newborn infants to certain mycobacterial, fungal and viral infections.

RECONSTITUTION OF CELLULAR IMMUNITY IN PATIENTS WITH SEVERE COMBINED IMMUNODEFICIENCY BY FETAL THYMUS TRANSPLANTATION AND TRANSFER FACTOR

Reconstitution of cellular immunity in 3 infants occurred following intraperitoneal fetal thymus transplantation and Transfer Factor therapy. In all 3, the earliest evidence of reconstitution was a rash consistent with graft vs host reaction (GVHR) with onset 10 to 14 days following transplant. Mild GVHR occurred in the 1- and 4-mo old infants who were apparently free of infection at the time of thymus transplantation from 12- and 14-week fetuses. These 2 infants are alive and well at age 2-½ yr and 11 mos. Severe GVHR occurred in the S-mo old infant following thymus transplant from a 16-week fetus; the infant was receiving therapy for pneumocystis carinii at the time of transplant. The child died 10 wks post-transplant with GVHR and pulmonary disease. The sequence of cellular reconstitution in all infants was lymphocyte response to allogenic cells, phytohemagglutinin, and T-cell rosette formation and occurred 3 to 12 wks following transplantation. Cell chimerism was detected by HL-A typing in 2 infants. Reconstitution of antibody-mediated immunity was not observed. Successful reconstitution in these patients, in contrast to earlier experience, was probably related to 3 factors: synergism between thymus and Transfer Factor, transplant of thymus within 1 hr after fetal abortion, and transplantation prior to severe infection.

PARTIAL RECONSTITUTION OF A PATIENT WITH CONGENITAL THYMIC DYSPLASIA BY FETAL TISSUE AND TRANSFER FACTOR

Attempts at immunologic reconstitution of patients with congenital thymic dysplasia have been disappointing. We have studied an 18 month old male with chronic history of mucocutaneous candidiasis (CMC), diarrhea, repeated infections and failure to thrive. He had a marked deficiency of T-cell functions with a decrease in circulating T-cells, absent cutaneous reactivity to skin test antigens and absent PHA responsiveness in vivo and in vitro. Although lymphopenic he had adequate numbers of circulating B-cells and plasma cells in his bone marrow aspirates. B-cell functions including levels of serum immunoglobulins, isohemagglutinins and pokeweed mitogen responsiveness were within the normal range. Implanted tissues from a female abortus of 16 weeks gestation restored in vivo and in vitro PHA responsiveness within 24 hours. Karyotypic and HL-A analyses demonstrated that chimerism had not occurred. In an attempt to augment persistently negative responses to Candida antigen, multiple doses of transfer factor (2.4 × 108 lymphocytes/dose) were administered. Peripheral T-cell rosettes increased from 5% to 40% without change in his response to Candida antigen or his clinical CMC. After eight months of continuing transfer factor therapy the patient has tripled his weight and remains clinically stable.

FAMILIAL IMMUNE DEFICIENCY AND LEUKODYSTROPHY: RECONSTITUTION WITH FETAL THYMUS IN A MILLIPORE CHAMBER

A 2 ½ year old male child (D.E.) with multiple congenital anomalies, severe psychomotor retardation, generalized seizures, chronic herpetie gingivostomatitis, overwhelming pneumococcal meningitis and sepsis was found to have a partial combined immunodeficiency. His female sibling (J. E.) who followed a similar course and who died at 4 ½ years of age was found to have sudanophilic leukodystrophy. During the course of his hospitalization, D. E. developed intractable diarrhea and was noted to have a decreased lymphoproliferative response to PHA, decreased T-cell rosette formation, a persistent lymphopenia and normal erythrocyte adenine deaminase (ADA) activity. Immunoglobulin therapy and parenteral hyperalimentation failed to alter his clinical course. Following transplantation of a 16-week fetal thymus enclosed in a millipore chamber there was prompt clearing of the herpetie lesions and cessation of the diarrhea within a few days after transplantation and an appearance of lymphocyte responsiveness to PHA one month later. Nine months after transplantation the patient remains infection-free and continues to display an intact cellular immunity. This report describes a previously unrecognized presentation of combined immune deficiency and suggests a new approach to therapy.

Letter: T-cell rosettes in thyrotoxic Graves's disease.

Letter: T-cell rosettes in thyrotoxic Graves's disease.