Transfer factor: perspectives in human and veterinary medicine.
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Animals↗
Biomedical subjects
C H Kirkpatrick
Publications and source records attributed to C H Kirkpatrick.
Altered immunity in hemophilia correlates with the presence of antibody to human T-cell lymphotropic virus type III (HTLV-III).
Twenty-nine heterosexual patients with hemophilia were investigated with histories, physical examinations, laboratory evaluations of immune function, delayed hypersensitivity skin tests, and assays for antibody to human T-cell lymphotropic virus type III (HTLV-III). Sixteen patients were HTLV-III antibody positive and 13 were HTLV-III antibody negative. No patient had the acquired immune deficiency syndrome (AIDS). Patients who had antibody to HTLV-III had received significantly more units and lots of factor concentrates in the preceding 5 years than those who did not have antibody. HTLV-III antibody-positive patients had significantly fewer total T cells (Leu-1 positive) and significantly fewer helper T cells (Leu-3 positive) than HTLV-III negative patients. Antibody-positive patients also had increased amounts of IgG and decreased thymidine incorporation in response to concanavalin A in vitro. There were no differences in in vitro lymphocyte responses to phytohemagglutinin (PHA), pokeweed mitogen, Candida, tetanus, or purified protein derivative (PPD), no significant impairments of gamma interferon or interleukin-2 (IL-2) production, and no anergy. Ten patients with antibody to HTLV-III had immunologic studies repeated 1 year after the original evaluation. A significant increase was seen in suppressor (Leu-2-positive) T cells but not in total T-cell or helper T-cell numbers, helper/suppressor ratios, or T-cell functional assays. We conclude that the immune abnormalities in hemophiliacs are the result of contact with HTLV-III but that these abnormalities may remain stable over prolonged periods.
Adult↗
The relationship of abnormalities of cellular immunity to antibodies to HTLV-III in homosexual men.
A comprehensive evaluation of the cellular immune system (total T-cell, helper cell, suppressor cell, and natural killer cell numbers; in vitro interleukin-2 production, T-cell responses to mitogens and antigens, serum beta 2 microglobulin levels, and delayed hypersensitivity skin tests) was performed on 36 HTLV-III seronegative and 16 HTLV-III seropositive healthy homosexual men, 48 asymptomatic homosexual men with the chronic lymphadenopathy syndrome, 41 patients with AIDS, and 29 heterosexual controls without any known risk factors for AIDS. Our studies demonstrate that HTLV-III seronegative homosexual men have normal cellular immunity and are comparable to heterosexual controls. The abnormalities of lymphocyte subsets observed in HTLV-III seropositive healthy homosexual men are comparable to subjects with chronic lymphadenopathy. Assays of lymphocyte function, with the exception of delayed type hypersensitivity (DTH) skin tests, are similar in each group except patients with AIDS. Subjects with chronic lymphadenopathy were less responsive to DTH skin tests and HTLV-III seropositive healthy homosexuals were comparable to chronic lymphadenopathy subjects. We conclude that immunologic abnormalities in homosexual men are attributable to infection with HTLV-III.
Acquired Immunodeficiency Syndrome↗
The regulatory effect of histamine on the in vitro synthesis of IgE.
The effect of histamine and its H1 and H2 antagonists, chlorpheniramine and cimetidine, on the in vitro, PWM-induced, synthesis of IgG and IgE was studied. Histamine had no effect, and cimetidine had a slight inhibitory action. In contrast, chlorpheniramine induced marked suppression of both IgE and IgG synthesis. This effect could not be attributed to drug-induced cytotoxicity. These results suggest that the modulatory effect of histamine on antibody production involves predominantly H1 receptors.
Cell Survival↗
The immunology of mycobacterial diseases.
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Antibody Formation↗
Altered excretion of modified nucleosides and beta-aminoisobutyric acid in subjects with acquired immunodeficiency syndrome or at risk for acquired immunodeficiency syndrome.
Urinary excretion of modified nucleosides and beta-aminoisobutyric acid, subsequently referred to as markers, was determined in populations of patients with acquired immunodeficiency syndrome (AIDS) or at risk for development of AIDS. Our results show that asymptomatic adult male homosexuals excreted elevated amounts of markers as compared to male heterosexuals. This aberrant excretion was more pronounced in asymptomatic adult male homosexuals with antibodies to HTLV-III. Significantly greater excretion of 1-methylinosine, N4-acetylcytidine, and N2-methylguanosine was observed in asymptomatic adult male homosexuals with antibodies to HTLV-III than in asymptomatic male homosexuals without antibodies to HTLV-III. Increased amounts of markers were also excreted by subjects with the generalized or chronic lymphadenopathy syndrome, AIDS related complex (ARC), or AIDS. In these subjects, the most pronounced differences between groups were between subjects with chronic lymphadenopathy syndrome and those with ARC; subjects with ARC excreted greater amounts of seven of the ten urinary markers. There were few differences between subjects with ARC and those with AIDS, Kaposi's sarcoma, or AIDS with opportunistic infections. This observation may be useful for identifying subjects who are at risk of developing AIDS. A prospective study to test this hypothesis is under way.
Acquired Immunodeficiency Syndrome↗
Interleukin-2 production by persons with the generalized lymphadenopathy syndrome or the acquired immune deficiency syndrome.
We measured production of interleukin-2 (IL-2) by phytohemagglutinin-stimulated peripheral blood mononuclear cells from 27 heterosexual persons, 43 asymptomatic homosexual men, 34 homosexual men with generalized lymphadenopathy syndrome (GLS), and 21 patients with acquired immune deficiency syndrome (AIDS). Asymptomatic heterosexual and homosexual subjects produced comparable amounts of IL-2, but 8 of 11 AIDS patients with opportunistic infections and two of three AIDS patients with both opportunistic infections and Kaposi's sarcoma failed to produce detectable amounts of IL-2; all seven AIDS patients with only Kaposi's sarcoma produced IL-2. The titer of IL-2 produced by the AIDS patients correlated with the percentage of helper T lymphocytes (Leu 3a+ cells) but not with the percentage of suppressor T lymphocytes (Leu 2a+ cells). This observation is interpreted as indicating that failure to produce IL-2 by AIDS patients is most likely due to depletion of IL-2-producing cells, although an abnormality of T-cell function has not been excluded. In addition, three of eight AIDS patients who did not produce IL-2 produced supernatants that inhibited growth of IL-2-dependent cells in the presence of IL-2. These observations suggest that measurement of endogenous IL-2 production may be important in selecting patients for therapy with IL-2.
Acquired Immunodeficiency Syndrome↗
The regulatory effect of macrophages on the in vitro synthesis of IgE.
The effects of indomethacin or macrophage-depletion on the in vitro unstimulated and pokeweed mitogen (PWM)-induced synthesis of IgG and IgE were compared. The effect on the unstimulated synthesis of IgG and IgE was similar, namely, no effect due to indomethacin and enhancement due to macrophage depletion. In contrast, the effect on PWM-induced synthesis was dissimilar. Macrophage depletion enhanced IgG but inhibited IgE production. The effect of indomethacin paralleled that of macrophage depletion suggesting the involvement of prostaglandins. It seems that the regulatory effect of macrophages is different in the IgE system compared with the IgG system.
Antigen-Presenting Cells↗
Regulatory effect of hydrocortisone on the in vitro synthesis of IgE by human lymphocytes.
The effect of different concentrations of hydrocortisone (HC) on the in vitro, pokeweed mitogen-driven synthesis of IgG and IgE by human lymphocytes was studied. HC had the same modulatory action on the production of both immunoglobulins. Two different effects were observed: the first is enhancement of Ig synthesis by low concentrations of HC (10(-7)-10(-4) M), and the second is inhibition of synthesis by higher concentrations due to lymphocytotoxic effect.
Cell Survival↗
Murine transfer factor. III. Specific interactions between transfer factor and antigen.
The interactions between dialyzable transfer factor and antigens have been studied. Incubation of transfer factor-containing dialysates from ferritin-sensitized mice or ferritin-coated plastic surfaces removed the antigen-sensitizing activity; incubations of the same preparations on cytochrome c-coated surfaces did not. Similar results were obtained when cytochrome c-transfer factor was studied. Incubation on cytochrome c-coated surfaces removed the activity, but incubation on ferritin-coated surfaces did not. Specific transfer factor activities could be recovered by elution with 8 M urea or acetonitrile. The finding of interactions between transfer factor and antigens provides evidence for a molecular basis of the specificity of the immunologic effects of transfer factor. This technique may also enable us to obtain amounts of specific material that are adequate for chemical analysis.
Animals↗
Murine transfer factor. II. Transfer of delayed hypersensitivity to synthetic antigens.
Synthetic polyaminoacid antigens were used to examine the specificity of transfer of delayed-type hypersensitivity with spleen cell dialysates in mice. Dialysates from GAT10-sensitized donors sensitized recipients to GAT10, but not GLA5 or cytochrome c. Dialysates from GLA5-sensitized donors sensitized recipients to GLA5, but not GAT10 or cytochrome c. We interpret these findings as consistent with the concept that passive transfer of delayed hypersensitivity with dialyzable materials is an immunologically specific event.
Animals↗
In vitro synthesis of IgE in atopic and nonatopic individuals: the effects of pokeweed mitogen, Staphylococcus aureus-derived mitogens, and cycloheximide.
We studied the production of immunoglobulin (Ig)E in cultures containing mononuclear cells obtained from atopic and nonatopic subjects. The two groups did not differ in their baseline production of IgE. Pokeweed mitogen (PWM) and three different products of Staphylococcus aureus: purified protein A, heat-killed formalinized bacteria, and double-formalinized bacteria--induced a significant increase in the in vitro production of IgE. Mononuclear cells from both atopic and nonatopic individuals were stimulated to the same degree by all four mitogens. The increased production of IgE by PWM was totally abolished by cycloheximide; hence it was due to de novo protein synthesis.
Adolescent↗
Host factors in defense against fungal infections.
The immune system contains multiple components that provide protection against specific groups of microorganisms. The degree of specialization of function is clearly illustrated in patients with immunodeficiency syndromes in whom the nature of the defect determines the sites of the infections and the susceptibility to certain organisms. Chronic mucocutaneous candidiasis is an especially dramatic illustration of the role of the T-lymphocyte system in defense against opportunistic fungal infections, especially of the skin and mucous membranes. There is considerable heterogeneity of the immune abnormalities in patients with chronic mucocutaneous candidiasis. The most consistent defects involve subnormal production of lymphokines by T-cells in response to Candida antigens. However, some patients have more global defects and are unresponsive to all antigens and may have reduced responsiveness to mitogens as well. Successful therapy of this infection requires a combination of treatments, including such antifungal drugs as clotrimazole, ketoconazole, or amphotericin B and correction of the underlying immune defect with such agents as transfer factor.
Acquired Immunodeficiency Syndrome↗
A microtiter assay for human monocyte activation by lymphokines.
This report describes a microtiter assay of human lymphokine activity based on lymphokine-induced increases in monocyte adherence to plastic surfaces. Supernatants were generated by stimulation of peripheral blood mononuclear cells with streptokinase/streptodornase or purified protein derivative. Monocyte adherence was measured by a 51chromium radioassay. The increased adherence was shown to be due to a soluble factor that was produced by antigen-stimulated mononuclear cells from donors who were responsive to the antigen but not by mononuclear cells from donors who were unresponsive. The factor was not dialyzable. The assay requires only 20 ml of peripheral blood and is easily automated and quantifiable, making it suitable for clinical laboratory use.
Cell Adhesion↗
Modulation of immunologic responses in nontuberculous mycobacterial infections with indomethacin.
We have previously reported that impaired in vitro cellular immunity is a common finding in patients with nontuberculous mycobacterioses and that the subnormal responses may be improved by indomethacin. Subsequently, we have studied the in vivo effects of indomethacin on cell-mediated immune functions of four patients with Mycobacterium avium-intracellulare infections. Prior to treatment none of the patients had delayed cutaneous reactions to purified protein derivative (PPD) of the tubercle bacillus, and their lymphocytes had subnormal in vitro proliferation responses to tuberculins from M. tuberculosis and M. avium-intracellulare and to phytohemagglutinin. The administration of indomethacin reconstituted both the in vitro lymphocyte responses and delayed cutaneous hypersensitivity. We propose that the impairment of T-cell dependent immune functions is mediated by a suppressive factor (or factors) that is a metabolic product(s) of the cyclooxygenase pathway of arachidonic acid metabolism. Preferential inhibition of this pathway with indomethacin allows the expression of cell-mediated responses.
Dermatitis, Atopic↗
The pathogenesis of trehalose dimycolate-induced interstitial pneumonitis. III. Evidence for a role for T lymphocytes.
Trehalose dimycolate, a glycolipid component of the cell walls of mycobacteria, induces interstitial pneumonitis and alveolar hemorrhages in C57BL/6 and C57BL/10 mice. Homozygous nude (nu/nu) mice of these backgrounds are not susceptible to this form of pulmonary injury. However, after administration of T-lymphocyte-enriched spleen cell preparations from syngeneic donors, homozygous nude mice become susceptible to trehalose dimycolate. The observations suggest that production of pulmonary lesions by this mycobacterial component is dependent on T lymphocytes. While the mechanisms are still under study, we propose that trehalose dimycolate can function as an activator of T lymphocytes and that products of activated T cells are responsible for production of the pulmonary lesions.
Animals↗
The pathogenesis of interstitial pneumonitis induced by trehalose dimycolate. II. Reserpine prevents formation of lesions.
A single intraperitoneal injection of 10 micrograms of trehalose dimycolate (TDM) produced interstitial and hemorrhagic pneumonitis in C57BL/6 mice. As a part of an investigation of a possible role for cell-mediated immunity in the pathogenesis of this disorder, we found that reserpine, 3 mg/kg, given before, at the same time, or on Day 5 after administration of TDM, significantly reduced development of interstitial pneumonitis by Day 7. Smaller doses were less effective. Administration of reserpine, 3 or 2 mg/kg, 1 to 3 days after administration of TDM was lethal to most mice. Reserpine has been shown to inhibit expression of cell-mediated immune responses in mice, probably by causing intercellular release and degradation of vasoactive amines. Inhibition of pulmonary lesions by reserpine in TDM-treated mice suggests that a similar mechanism may be involved in the pathogenesis of TDM-induced lung injury.
Animals↗
The acquired immunodeficiency syndrome and a trimethoprim-sulfamethoxazole adverse reaction.
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Acquired Immunodeficiency Syndrome↗