Pecht M

Thymic hormones: inducers and

The first evidence of the thymuss pivotal role in immune, function was gathered by experiment and clinical observation more than 20 years ago. Nathan Trainin and his colleagues have helped to establish the link between the endocrine mechanism of the thymus gland and its immunological function. Here they describe the chemistry, biochemistry, and biological effects o f hormones isolated from or originating in the thymus(1-3).

Immunologic dysregulation in a patient with familial hemophagocytic lymphohistiocytosis

A 6‐year‐old Jewish Iranian girl with familial hemophagocytic lymphohistiocytosis (FHLH) is described. The course of the disease fluctuated with partial initial response to antibiotics, steroids, and supportive treatment. Subsequent cytotoxic treatment, including VP‐16, Velban (vinblastine sulfate), and methotrexate (MTX) controlled the disease for a few months but the child died with a clinical picture of meningocephalitis 1.5 years later. Benign‐looking lymphohistiocytic infiltrates with varying degrees of hemophagocytosis were present in the bone marrow, pleural effusion, cerebrospinal fluid (CSF), liver, and brain. Clinical and laboratory evidence of immunologic dysregulation during the disease could be demonstrated. Frequent and intense viral and bacterial infectious diseases were encountered. The laboratory examination most consistently found was the absence of natural killer (NK) cell activity against K562 target cells. The impaired activity of NK cells persisted during all stages of the disease including remission, although NK cell numbers, determined morphologically and immunophenotypically (by Leu‐11, Leu‐7), were normal. Natural killer activity could not be restored by interferon. Moreover, the interferon system appeared to be intact. Impaired monokin interleukin 1 (IL‐I) production by peripheral blood monocytes was found and cound not be restored by indomethacin. Lymphopenia, a mild decrease in T4 numbers, and subsequently, decreased proliferative response to mitogens was noted. Elevated immunoglobulin levels were found during exacerbations and viral episodes, at times accompanied by the presence of auto‐antibodies. The exaggerated fatal lymphohistiocytic response typical for FHLH could be attributed to a underlying genetic pathologic dysregulation of the various immunological response pathways.

T Lymphocyte Subsets and Function in the Peripheral Blood of Patients with Urological Cancer

The phenotypic distribution and immune reactivity of T lymphocyte subpopulations from peripheral blood of 50 patients with urological cancer were determined. Included were 36 patients with bladder transitional cell carcinoma, 7 patients with renal cell carcinoma and 7 patients with prostatic carcinoma. Thirty-eight age-matched patients with benign urological disease served as controls. A depression in immune competence was found in the group of male patients with infiltrating bladder cancer. In more than 50% of the patients with infiltrating bladder carcinoma, the T helper (CD4) subset was reduced with a concomitant inversion in the CD4/CD8 ratio and impairment in the T cell function as determined by the ability to proliferate upon phytohemagglutinin and concanavalin stimulation. Patients with superficial bladder carcinoma, as well as those with renal cell carcinoma had an immune profile similar to that of the control group. The group of patients with prostatic carcinoma had higher mean CD4/CD8 ratios than the control group, resulting from decreased suppressor/cytotoxic cells. Our results have indicated that the characterization of T cell subset and lymphocyte activity correlated well with the histopathologic state of patients with bladder carcinoma. Thus, the determination of the CD4/CD8 ratio may prove a valuable method for monitoring patients with bladder carcinoma, in addition to serial urine cytology, random urothelial biopsies and flow cytometry.

Hydrolysis of alanine oligopeptides by an enzyme located in the membrane of Mycoplasma laidlawii

Abstract Membranes obtained from Mycoplasma laidlawii and whole cells suspended in an isotonic salt solution cleva the N(α)- termional l -alanine residue of oligoalanine peptides of the general formula Ala( l )-[Ala( l )-Ala( d )]n, n = 2,4,8 . The intact cells were found to be impermeable to l -alaine when suspended in an isotonic salt solution Entry of l -alanine into the cells was observed only whens suspended in the appropriate growth medium.

Water soluble polycationic derivatives of trypsin and chymotrypsin - preparation and properties

Abstract Water-soluble polycationic derivatives of trypsin and chymotrypsin were prepared by the enzyme initiated polymerization of the a-N-carboxyanhydride of σ-triflouroacetyl- L -ornithine.Poly- L -ornithyl trypsin (POT) and poly- L -ornithyl chymotrypsin (POCH), containing 30–50 bound ornithine residues per mole of enzyme, were obtained upon removal of the protecting group. Branched poly- L -ornithyl poly- L -ornithyl trypsin (POOT) was obtained by further polymerization of the a, N-carboxyanhydride via initiation with POT and subsequent hydrolysis of the trifluoroacetyl groups. The POOT derivatives contained about 100–150 bound ornithine residues per enzyme molecule. The pH-esteratic activity profiles of the polycationic enzymes, determined at different ionic strengths, reflected the influence of the electrostatic field induced by the attached polyelectrolyte chains. Similarly, the different activity pattern towards a basic protein, compared to the native enzyme, was also attributed to electrostatic interactions.

Immunoreconstitution of T-cell impairments in asymptomatic male homosexuals by Thymic Humoral Factor (THF)

The feasibility of using Thymic Humoral Factor (THF) for immunomodulation in asymptomatic male homosexuals was evaluated in a study on fifteen subjects with T-cell impairments, selected on the basis of a 2SD reduction in T helper/inducer (T4+) cells and one additional lymphocytic defect. Following two biweekly courses of treatment, mean relative increments of T4+ (P less than 0.002), T3+ (P less than 0.02) and total lymphocyte (P less than 0.05) populations of the group receiving THF (n = 7) were significantly increased when compared to the placebo group (n = 8). In addition, a transient increase in T4+ lymphocytes was observed after the first course in the two individuals of the THF-treated group who were seropositive for HTLV-III/LAV but not in those who were seronegative. No difference was found between the groups in fluctuations of serum interferon (IFN) or proliferation of peripheral mononuclear cells to mitogens. The results of this limited trial demonstrate that THF is capable of correcting T-cell impairments that may predispose asymptomatic homosexuals to infection by HTLV-III, without affecting IFN production. These findings suggest that future strategies for AIDS prevention in high-risk groups should include institution of large controlled trials in immunodeficient, asymptomatic, HTLV-III/LAV-seronegative male homosexuals to study the potential of selective immunoreconstitution as a preventive measure against HTLV-III/LAV infection.

Thymic Humoral Factor-γ2 (Thf-γ2) Immunotherapy Reduces the Metastatic Load and Restores Immunocompetence in 3LL Tumor-Bearing Mice Receiving Anticancer Chemotherapy

AbstractIn mice bearing immunogenic tumors, adding thymic humoral factor-γ2 (THF-γ2)1 immunotherapy as an adjunct to anticancer chemotherapeutic regimens not only potentiates the antitumor activity of each drug but also repairs tumor/chemotherapy-induced damage to T-cell populations and functions. The Lewis lung carcinoma (3LL) is a weakly immunogenic, highly metastatic tumor in C57BL/6 mice. To investigate whether the immunoregulatory octapeptide is also effective against a tumor that does not elicit an antitumor immune response, we assessed the effect of combination THF-γ2 immunotherapy and chemotherapy in 3LL-bearing mice. The results indicate that THF-γ2 combined with either Melphalan or 5-Fluorouracil was more effective in reducing metastatic load than either chemotherapeutic drug alone and was characterized by massive infiltration of lymphatic cells. The combined chemoimmunotherapy treatment also prolonged the survival time in all treated animals and repaired T-cell defects and impaired in vitro cel...

Therapy of a fatal murine cytomegalovirus infection with thymic humoral factor (THF-γ2) treated immune spleen cells

Infection of mice with murine cytomegalovirus (CMV) presents a model for the study of the role of the immune system in the pathogenesis of human CMV. We performed adoptive transfer experiments to evaluate the prospects for enhancing the anti‐viral potential of murine CMV immune spleen cells by THF‐γ2. Adult BALB/c mice resistant to murine CMV become highly susceptible following immunosuppression by cyclophosphamide. Recipient mice were injected with murine CMV and cyclophosphamide concomitantly, and 24 h later adoptive transfers of syngeneic immune spleen cells were performed. We showed that passive transfers of murine CMV immune spleen cells prevented the development of a fatal disease in 38% of the recipient mice. Daily injections of murine CMV immune donor mice with THF‐γ2 enhanced considerably (93%) the therapeutic potential of virus‐specific immune cells. These experiments provide direct evidence for the antiviral capacity of THF‐γ2 through its immunomodulatory effect on immune T cells.

Impaired immune regulation in children and adolescents with hemophilia and thalassemia in Israel

The immune function was assessed in 22 children, adolescents and young adults with asymptomatic hemophilia, and 15 with thalassemia, in Israel. Five patients with hemophilia and two with thalassemia were found to be severely abnormal, having cutaneous anergy, very low T-helper cells, elevated T-suppressor cells, inverted T-helper/suppressor ratio, reduced response to mitogens and antigens, and nonfunctional NK cells. Four of the five hemophilia patients exhibited profound lymphopenia also. Decreased T-helper and mildly elevated T-suppressor cells with inverted T4/T8 ratio were observed in the hemophiliacs as a group. In the severe group, the reduction in T-helpers and T4/T8 ratio was more pronounced. The thalassemics as a group were found to have increased numbers of T-suppressor cells with decreased T-helper cells in those with intact spleen only. Both groups studied were found to have elevated IgG levels and low natural killer (NK) activity and normal response to mitogens. Cutaneous anergy was found to be a reliable indication for severe T-cell dysfunction and may serve as an early indication of impending AIDS. These results indicate that patients with hemophilia and with heavily hyper-transfused thalassemia may be at increased risk of AIDS as they approach adolescence.

THF-γ2, a thymic hormone, increases immunocompetence and survival in 5-fluorouracil-treated mice bearing MOPC-315 plasmacytoma

SummaryThe effect of the thymic hormone, THF-γ2, on the immunocompetence of 5-fluorouracil (5-FU)-treated BALB/c mice, bearing MOPC-315 tumor, was examined. Treatment of noninoculated or tumor-bearing mice with THF-γ2 after 5-FU injection, resulted in an increase in the antibody response to sheep red blood cells and in the allogeneic response in spleen cell cultures and had no effect on the concanavalin-A-induced interleukin-2 secretion beyond that caused by 5-FU alone. Treatment with either 5-FU alone or 5-FU and THF-γ2 resulted in restoration to normal values of Lytl- and L3T4-positive populations in tumor-bearing mice. THF-γ2 prolonged the survival time of mice bearing MOPC-315 tumor beyond that observed in mice treated with 5-FU alone.