Denis R. Burger

Depressed lymphocyte responsiveness in autistic children.

Although there are associations linking autism with prenatal rubella, cytomegalovirus, syphilis, and varicella, the etiology of the autistic state remains obscure. Host defense against the etiologic agents postulated to be responsible for the autism-associated syndromes is believed to be primarily of the cell-mediated type. In this preliminary study, cellular immune function was assessed in vitro by phytohemagglutinin (PHA)stimulation of lymphocyte cultures. Twelve autistic children and 13 control subjects were compared. The autistic group exhibited a depressed lymphocyte transformation response to PHA when compared to the control subjects (p<.01).

Precursor frequency of antigen-specific T cells: effects of sensitization in vivo and in vitro.

Limiting dilution analysis (LDA) of primary lymphocyte cultures was used to determine the frequency of keyhole limpet hemocyanin (KLH)-specific precursors in the peripheral blood of unimmunized individuals. The KLH-specific precursor frequencies ranged from 1:150,000 to 1:340,000. In contrast, frequencies of KLH-specific cells in the blood from immune donors ranged from 1:25,000 to 1:42,000. LDA of KLH-stimulated primary cultures indicated that the frequency of KLH-specific cells increased with time in culture reaching a four- to fivefold expansion relative to the frequency obtained prior to culture. The data presented suggest that the enhanced kinetics of secondary T-cell responses observed after in vitro sensitization are due to a decrease in the proportion of lymphocytes which exhibit a suppressor phenotype.

Human transfer factor activity in the guinea pig: Absence of antigen specificity☆

Abstract Human transfer factor of known antigen specificity was used to induce skin-test reactivity in strain 13 guinea pigs. This reactivity is reproducible, is dependent upon preexposure of the animal to subsensitizing doses of antigen, persists for at least 14 weeks, and is reflected in some cases by antigen-induced lymphocyte transformation. The skin test response in guinea pigs does not reflect the antigen reactivities of the human TF donor; this suggests that in guinea pigs the TF may augment a low level of sensitization produced during the priming step.

All KLH preparations are not created equal

Abstract Keyhole limpet hemocyanin (KLH) preparations used for dermal testing in human volunteers may contain factors which elicit false positive reactions. These factors can be associated with the hemolymph collection procedure and possibly to a change in collection beds by the limpet supplier. Rapid collection of hemolymph from animals obtained from specified limpet beds resulted in KLH which produced negligible dermal reactivity in normal individuals.

Delayed type hypersensitivity to gangliosides in the Lewis rat

Systematic study of the immunologic properties of gangliosides has been hampered by the lack of a suitable assay. In this study, significant delayed type hypersensitivity reactions to gangliosides were observed in Lewis rats immunized with whole guinea pig spinal cord (GP-SC) in complete Freunds adjuvant (CFA). The reaction was manifested by an increase in ear thickness after intradermal injection of a mixture of gangliosides and methylated bovine serum albumin (mBSA). No responses were observed to either gangliosides or mBSA alone. The reaction to gangliosides increased after immunization, persisted for 48 h, and was characterized by perivascular infiltration of mononuclear cells. Further evidence for a cellular response was demonstrated by the transfer of ganglioside-specific ear swelling by cultured spleen cells. The response to gangliosides was not due to contamination with myelin basic protein (BP) since no reaction to gangliosides was observed in GP-BP/CFA-immunized rats, and no reaction to BP was observed in ganglioside/CFA-immunized rats. In BP-immunized rats, responsiveness to BP persisted after recovery from clinical EAE for at least 60 days. However, no response to gangliosides was observed in BP-immunized animals after recovery from clinical EAE, suggesting the lack of autosensitization to gangliosides due to the disease process itself.

Lymphocyte suppression associated with alpha globulin changes in cellular immunity

Abstract Sensitization of guinea pigs to 2,4-dinitrofluorobenzene is accompanied by increases in alpha globulins determined electrophoretically. During sensitization, lymphocyte responses were measured in vitro by mitogen induced 3H-thymidine uptake in whole blood cultures and in vivo by dermal skin reactivity. Following 5 days of dinitrofluorobenzene sensitization alpha globulins were elevated and lymphocyte transformation to phytohemagglutinin, pokeweed mitogen, and concanavalin A was significantly suppressed. When the alpha globulins returned to normal levels following sensitization, lymphocyte responses returned to pretreatment values. Antigen induced lymphocyte responsiveness was also suppressed concomitant with elevations in alpha globulins. Tuberculin sensitive guinea pigs responded poorly to PPD in vitro and in vivo during DNFB sensitization. It is suggested that increases in alpha globulins detected during the development of cellular immunity are associated with immunosuppression.

Virus-associated deficiencies in the mitogen reactivity in celebes black macaques (Macaca nigra)

Celebes black macaques (Macaca nigra) with a history of diabetes mellitus, recurrent bacterial and protozoal infections, diarrhea, anemia, weight loss, anorexia, and a high mortality were studied to determine their immune status. Two groups of monkeys, healthy and unhealthy, were formed on the basis of a clinical assessment. The proliferative response and the pokeweed-mitogen-induced polyclonal IgG response of peripheral blood mononuclear cells of unhealthy monkeys were significantly less than the responses of healthy monkeys. The percentage of HLA-DR+ cells varied greatly in unhealthy monkeys. The OKT4/OKT8 ratios of unhealthy monkeys were generally greater than the ratios of healthy monkeys. Unhealthy monkeys usually had smaller percentages of OKT8+ cells than did healthy monkeys. The two groups of monkeys were examined for the presence of a syncytial forming retrovirus by a coculture assay involving Raji cells, a human B lymphoblastoid cell line. A type D retrovirus was detected in the unhealthy group but not in the healthy group. Retroperitoneal fibromatosis was detected in several monkeys in the unhealthy group.

Alpha globulin changes during the development of cellular immunity

Abstract Hartley guinea pigs were sensitized to 2,4-dinitrofluorobenzene, Mycobacterium tuberculosis H37RA , and allogenic skin. During the development of these sensitivities, serum alpha globulin changes were detected by polyacrilamide gel disc electrophoresis. Electrophoretic region 4 (alpha globulins) increased, then subsided, concomitant with the development of cellular immunity. Skin testing did not seem to influence alpha globulin levels in sensitized animals. However, high alpha globulin levels decreased skin test responsiveness. It is suggested that the increased alpha globulin noted here is immunoregulative alpha globulin (IRA).

TRANSFER FACTOR IMMUNOTHERAPY IN CANCER

Publisher Summary This chapter reviews results of experiments conducted to study transfer factor (TF) immunotherapy in cancer. The chapter states that the rationale for the use of TF in antitumor therapy is that certain persons are immune to same tumor antigens and that TF isolated from those individuals will activate specific antitumor activity in cancer patients. The experimental team selected patients for the study who had histologically proven cancer usually with widespread tumor dissemination and had failed to respond further to conventional therapy. Thirteen patients showed a clinical response to transfer factor in terms of regression of the tumor, arrest of metastases or relief of pain. Additionally, it was observed during tests that none of the patients who responded favorably to TF were blocked in culture when they entered the study. The examination results revealed that dermal responses to selected tumor antigens were examined in many of the TF recipients. The specificity of the dermal reactions was determined by dermal responses to different tumor antigen preparations in patients with histologically distinct tumors.

The effects of plasma from guinea pigs with tumor on PHA stimulated lymphocyte cultures.

Abstract Strain 13 guinea pigs with a transplanted, 3-methylcholanthrene induced fibrosarcoma produced a plasma factor that inhibited PHA induced blastogenesis of lymphocyte cultures from normal and tumor animals. The suppressive activity was not cytotoxic, was not adsorbed from plasma by lymph node cells, and was a noncompetitive inhibitor of PHA activation. The tumor plasma could not inhibit the uptake of [ 3 H]thymidine if added during the period of maximal DNA synthesis, which suggested that the suppressive factor acts most effectively on metabolically resting cells. This nonspecific suppressive factor may represent an important mechanism for allowing rapidly progressive tumors to escape immunological destruction.