Nelson F. Mendes

Cell‐mediated immunity in patients with carcinoma. Correlation between clinical stage and immunocompetence

Cell‐mediated immunity (CMI) was evaluated in 82 patients with non‐lymphoid tumors by in vivo and in vitro methods. These included skin test with ubiquitous antigens, 2,4 dinitrochlorobenzene (DNCB) sensitization, determination of T and B peripheral blood lymphocytes, and lymphocyte response to phytohemagglutinin (PHA). The patients were divided into two groups: those with localized and those with disseminated disease (LD and DD). The patients with LD showed no significant differences in CMI when compared with normal controls. The patients with DD showed various defects in CMI when compared with controls and patients with LD. There were significant differences in the response to DNCB, and streptokinase‐streptodornase (SKSD) was the most discriminative of the skin‐test antigens. The response to PHA was greatly depressed in patients with DD, whether in the presence of autologous or homologous plasma; in some patients a factor inhibiting to blastogenesis was detected in the serum. In patients with DD, a T‐cell lymphopenia was observed. These data showed a correlation between immunocompetence and clinical stage.

Restorative effect of normal human serum, transfer factor, and thymosin on the ability of heated human lymphocytes to form rosettes with sheep erythrocytes

Human lymphocytes submitted to heating at 45°C for 1 hr liberate receptors for sheep erythrocytes (E) in the supernatant (SHL) and their ability to form rosettes with E is abolished. The rosetting property is partially restored by incubation of heated lymphocytes with SHL, normal human serum (NHS), transfer factor (TF), and thymosin (TH). Treatment of E with SHL, normal human serum dialysate (NHSD), TF, and TH enable these cells to bind lymphocytes deprived of their receptors for E by previous heating. These methods provide a new in vitro assay for TF and TH. The amount of receptors for E in NHS can also be estimated by this assay.

Influence of cholecalciferol (Vitamin D3) on the course of experimental systemic lupus erythematosus in F1 (NZBxW) mice

The course of systemic lupus erythematosus (SLE), an autoimmune disease, is markedly affected by hormones such as estrogen and prolactin. It is well known that heavy exposure to sunlight has deleterious effects on SLE, triggering episodes of the disease. Classical explanations for this occurrence suggest that UV radiation damages DNA, which becomes immunogenic, or induces exposure of the Ro antigen in keratinocytes. In recent years, it has been shown that vitamin D3 has important effects on the immune system. Thus, we proposed an alternative hypothesis, suggesting that UV radiation, by promoting vitamin D3 synthesis, could be a factor aggravating the course of SLE after exposure to sunlight. To test this hypothesis, we injected F1(NZBxW) mice, which are prone to developing SLE, with vitamin D3, and we demonstrated a worsening of the histopathological findings in the kidney. J. Clin. Lab. Anal. 14:91–96, 2000.

Lymphocyte cultures and skin allograft survival in patients with South American blastomycosis

Abstract Lymphocyte cultures with phytohemagglutinin (PHA), skin allograft survival, intradermal tests with microbial antigens, and sensitization to dinitrochlorobenzene (DNCB) were performed in 10 patients with South American blastomycosis. The lymphocyte stimulation in vitro was depressed in 6 of the patients. Exposure to DNCB resulted in sensitization in 3 of 10 patients. Among the 7 DNCB-negative patients, Mast transformation was depressed in 6, and in 2 of these there was prolonged skin allograft survival. The results suggest a severe impairment of delayed hypersensitivity in some patients with South American blastomycosis.

Cellular immunity in squamous cell carcinoma of the uterine cervix

The thymus-dependent immunity of 42 patients with SCCC was evaluated by: delayed cutaneous reactions to ubiquitous antigens, DNCB sensitization, and lymphocyte response to PHA. In addition, T and B lymphocytes were detected in peripheral blood and in tumor sections, by adherence to E and HEAC. Depressed CMI was more intense in patients with disseminated disease, although a premature impairment of CMI was observed in some patients with initial-stage tumors. The absolute number of peripheral T lymphocytes showed association with both cutaneous reactions and PHA response. However, there appeared to be no significant correlation between the stage of the tumor and the pattern of adherence of E or HEAC to the biopsies.

Immunosuppressive effect of soluble E receptors in uremic serum

Abstract The effect of serum and urine from uremic patients upon the proliferative response of lymphocytes to phytohemagglutinin and to allogeneic cells was investigated. Addition of uremic serum dialysate, to cultures performed in the presence of normal human serum, promoted a significantly higher inhibition of blastogenesis, compared with the addition of normal serum dialysate. Uremic urine and its dialysate induced degrees of depression upon the lymphocytes proliferative response equivalent to those observed with normal urine and normal urine dialysate, respectively. Absorption with sheep erythrocytes (E) removed the inhibitory effect from uremic serum and diminished significantly the inhibition induced by uremic urine. We concluded that accumulation of soluble E receptors, in uremic serum, is the main cause of its immunodepressive properties.

Cell-mediated immunity in leprosy and transfer of delayed hypersensitivity reactions

Abstract Eighty-nine patients with leprosy, 65 classified as lepromatous and 24 as tuberculoid, were examined in this study. Skin test responses to protein antigens and dinitrochlorobenzene (DNCB) were depressed in lepromatous patients compared to controls. Tuberculoid patients did not exhibit a significant depression to microbial antigens, but they showed a definite depression in the ability to be sensitized with DNCB. The transfer of delayed hypersensitivity reactions to tuberculin, trichophytin, and lepromin (Fernandez and Mitsuda reactions) was accomplished in lepromatous and indeterminate leprosy patients using viable lymphocytes from donors presenting positive reactions to these antigens. The lepromin reaction was also transferred to patients with South American blastomycosis and cutaneous leishmaniasis. The positive reactions of adoptive immunity were confirmed by histologic examination of skin biopsies.

Human T lymphocyte receptor for sheep erythrocytes: Characterization of a specific antiserum and its application in the detection and quantitation of the receptor in a soluble form

Abstract An anti-human T lymphocyte serum specific to the receptor for sheep erythrocytes (E) was produced by immunizing sheep with the complex autologous E-soluble E receptor (ER s ). The soluble receptor (R s ) was obtained by heating human lymphocytes at 45 °C for 1 hr. The anti-R s serum has been shown to inhibit E-rosette formation, to be cytotoxic to T cells, to identify T lymphocytes by indirect immunofluorescence, and to stimulate blastogenesis. The reaction of anti-R s with R s was directly demonstrated by two newly developed methods: agglutination of complexes formed by the treatment of formolized E with R s (EFR s complexes) and adhesion of a protein A producer strain of Staphylococcus aureus to EFR s treated with anti-R s . The anti-R s antibodies could be neutralized by R s present in supernatant of heated peripheral lymphocytes, inhibiting the above reactions and therefore providing methods to quantitate R s in biological preparations. The importance of these assays is that R s plays an immunoregulatory activity, and high levels of R s in serum are associated with depressed cell-mediated immunity.

Immunoregulation of the proliferative response of lymphocytes by soluble E receptors

Abstract The role played by soluble human T-lymphocyte receptors for sheep erythrocytes (E) upon the proliferative response of lymphocytes was investigated. Preparations containing soluble E receptors, e.g., normal human serum dialysate (NHSD) and leukocyte dialysate containing transfer factor (TF) were added to cultures performed in the presence of normal human serum. In most of the cultures stimulated by allogeneic cells or by phytohemagglutinin (PHA), the addition of these preparations induced inhibition of the [3H]thymidine uptake. Previous absorption with E abolished or diminished significantly this inhibitory effect. Addition of NHSD absorbed with E restored the proliferative response in mixed leukocyte cultures performed in medium containing dialyzed normal human serum instead of NHS. The immunoregulation exerted by soluble E receptors upon the proliferative response of human lymphocytes seems to be more clearly expressed in the response to allogeneic cells than in the response to PHA.

Monocyte function in patients with solid neoplasms during immunotherapy with Corynebacterium parvum.

The present studies were performed in order to evaluate monocyte function in patients with solid neoplasms before and after administration of C. parvum. The results demonstrate that monocytes from cancer patients display increased numbers of C3 and Fc receptor sites after administration of C. parvum. It is concluded that characterization of monocyte receptor activity may be helpful in monitoring the effects of immunotherapy in the immune system.