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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell-mediated immune responses to cytomegalovirus infections were studied to define mechanisms for deficient effector T-cell responses in patients with the acquired immunodeficiency syndrome (AIDS). Progressive cytomegalovirus infection is common in such patients and is accompanied by a failure to develop HLA-restricted cytotoxic T-cell responses. The mechanism for the cytotoxic T-cell deficiency is presumably the basis for susceptibility to opportunistic infections. Precursors to these effector cells circulate in the peripheral blood of patients, but maturation of these cells into cytotoxic T cells is arrested during an interleukin-2-dependent phase. Production of interleukin-2 by lymphocytes from patients with AIDS is deficient because sera from these patients contain an inhibitor of interleukin-2 production. Excess suppressor cell activity does not appear to account for this deficient production. Studies of the source of the serum inhibitor should provide insights into the pathogenesis of AIDS and possible leads for effective treatment.
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PMID:Mechanisms of T-cell functional deficiency in the acquired immunodeficiency syndrome. 299 4

Although effective therapies are available for many of the infections and tumors that occur in patients with the acquired immunodeficiency syndrome (AIDS), no therapy exists for the underlying immunodeficiency. Three approaches used to treat this immunodeficiency have included wholescale immune replacement through lymphocyte transfers, bone marrow transplantation, and thymic implantation; immunologic enhancement with biologic-response modifiers, such as gamma interferon, interleukin-2, and some drugs; and antiretroviral therapy. Because of the persistence of the etiologic virus, both immune replacement and enhancement will probably be ineffective unless effective strategies are developed against the virus. Agents that have shown antiviral activity in vitro which are currently in clinical trials include suramin, heteropolyanion-23 (HPA-23), ribavirin, and alpha interferon. Foscarnet and monoclonal antibodies have yet to enter clinical trials in the United States. It is still too early to tell if any of the antiviral agents will prove of value in the management of patients with AIDS.
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PMID:Immunologic reconstitution in the acquired immunodeficiency syndrome. 299 5

A cell-line, designated LSA-1, was derived from a thymic lymphosarcoma that occurred in a cat with experimentally induced feline leukemia virus (FeLV) infection. LSA-1 cells possessed surface receptors and antigens of normal T-lymphocytes, but were unresponsive to interleukin-2 stimulation. The LSA cell-line was found to constitutively produce and release an interferon into the culture supernatants. Production of this interferon was enhanced in certain clones of the original LSA-1 cell lines. The interferon produced by LSA-1 cells and some of its clones was compared to the standard alpha, beta, and gamma interferons of cats. Unlike alpha and beta interferons, which were acid, SDS, and heat stable, LSA interferon was acid labile and SDS and heat stable. In comparison, standard feline gamma interferon was acid, SDS, and heat labile. LSA interferon had a molecular weight of 20,000 daltons, compared to 17-19,000 daltons for gamma, 19-25,000 for beta, and 25-45,000 daltons for alpha interferons. Standard feline interferons were active only on cat cell lines, with the exceptions of alpha interferon, which also reacted with MDCK canine cells. LSA interferon resembled the standard feline alpha interferon because it also reacted with feline and canine cells. It was concluded that LSA interferon was an atypical acid labile alpha interferon, resembling in this respect the abnormal alpha interferon seen in humans with AIDS and SLE, and mice with retrovirus infections. LSA-1 cells produced high levels of FeLV structural proteins but very little infectious virus. This effect was due to endogenously produced interferon; LSA cell clones that were selected for low interferon production produced much higher levels of infectious FeLV than parent cells or clones selected for high interferon production. Cat cells pretreated with LSA or with standard feline alpha and beta interferons, and then infected with FeLV, produced high levels of FeLV proteins but very little infectious virus.
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PMID:A feline retrovirus induced T-lymphoblastoid cell-line that produces an atypical alpha type of interferon. 300 26

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.
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PMID:Altered immunity in hemophilia correlates with the presence of antibody to human T-cell lymphotropic virus type III (HTLV-III). 300 63

Sera from 22 patients with either lymphadenopathy syndrome (LAS), acquired immune deficiency syndrome (AIDS)-related complex (ARC), or acquired immune deficiency syndrome were examined for their effect on the interleukin-2 (IL-2)-induced proliferative response of an IL-2-dependent cytotoxic T-cell line, CTL-20. All of the patient sera included in this study were positive for the presence of antibodies against human T-cell lymphotropic virus type III (HTLV-III) as determined by an HTLV-III-specific enzyme-linked immunosorbent assay (ELISA). Eighteen of the 22 patient sera examined (81.8%) exhibited at least a modest suppressive effect on the proliferative response of CTL-20 cells. The inhibitory effect was dose-dependent and varied in intensity for each individual serum. In many cases, the magnitude of suppression was absolute in that it totally abrogated IL-2-induced DNA synthesis. Normal human serum (NHS) exerted no suppressive influence on the IL-2-induced proliferative response of identical control cultures. This same panel of 22 patient sera exhibited no significant inhibitory effects on the levels of protein synthesis in cultures of a non-IL-2-dependent human T-cell line, CCRF-HSB-2, indicating that the suppressive effect was not mediated by nonspecific serum cytotoxicity. The inhibitory effect of patient sera in the IL-2-dependent target cell assay correlated with the ability of these same sera to suppress the mitogen-induced proliferative response of normal human peripheral blood lymphocytes (PBL). These observations are particularly striking in view of the recognized defects of IL-2-dependent effector T-cell functions in AIDS.
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PMID:Inhibition of interleukin-2-induced T-cell proliferation by sera from patients with the acquired immune deficiency syndrome. 300 64

Infectivity was assayed by infecting human T-lymphocytes, H9, Molt-4, and MT-4 cells with different strains of AIDS viruses (HTLV-III, LAV, ARV, and YU viruses). Human T-lymphotropic virus type-III (HTLV-III), lymphadenopathy-associated virus (LAV), and AIDS-associated retrovirus (ARV) were able to infect all kinds of target cells tested and to induce virus-specific antigens, whereas Japanese isolates, YU viruses, infected only interleukin-2-dependent human T-lymphocytes. Long-term propagation of the YU viruses and pretreatment of the cells with Polybrene did not allow the YU virus to produce viral antigens by infecting H9, Molt-4, and MT-4 cells. Thus, YU viruses have a rather narrow host range as compared with HTLV-III, LAV, and ARV. These different infectivities may be reflected in the progress and symptoms of AIDS in vivo.
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PMID:Narrow host range of AIDS-related retroviruses (YU-1, 2, 3, 4) isolated from Japanese hemophiliacs: inability to infect H9, Molt-4, and MT-4 cells. 301 50

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.
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PMID:The relationship of abnormalities of cellular immunity to antibodies to HTLV-III in homosexual men. 301 81

Peripheral blood lymphocytes of patients with AIDS are generally anergic to stimulation by lectins or by alloantigens. We have succeeded in demonstrating that the lymphocytes of six AIDS patients, with histories of herpes simplex virus (HSV)-induced genital, anal and/or oral lesions, retained functional specificity with regard to HSV antigens. This was accomplished by treating patient lymphocytes with OKT8 monoclonal antibodies, in the presence of complement, to yield a cell population that was partially responsive to phytohaemagglutinin (PHA). Enhanced proliferation was obtained in the presence of exogenous interleukin-2, which was also employed to foster the growth of these cells over several generations. Lymphocytes derived from these AIDS patients, and maintained in vitro as described, were specifically stimulated in proliferation assays by a HSV antigen preparation in six of the ten cases studied.
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PMID:Specific stimulation of lymphocytes from patients with AIDS by herpes simplex virus antigens. 302 41

We investigated Epstein-Barr virus (EBV)-specific T cell responses in homosexual men with, and at risk for, AIDS. We studied healthy laboratory workers, healthy homosexual men, and patients with AIDS-related complex or AIDS. The cytotoxic activity, absolute number of T4 lymphocytes, and interleukin-2 (IL-2) production decreased, whereas the relative number of Ia+ lymphocytes increased with the extent of infection with the human immunodeficiency virus (HIV). Cytotoxic activity correlated positively with the number of T4 lymphocytes (r = .56, P less than .001) and the amount of IL-2 produced (r = .47, P less than .01) but not with interferon production. Recombinant IL-2, but not gamma interferon, could restore cytotoxic T cell activity to control levels in patients with early HIV infection. EBV-specific serological studies paralleled the T lymphocyte investigations. The increased EBV activity observed in progressive HIV infection may be related to a diminution in the auto-reactive population of the T4 lymphocyte subset and may be amenable to IL-2 reconstitution.
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PMID:Effects of human immunodeficiency virus on the cellular immune response to Epstein-Barr virus in homosexual men: characterization of the cytotoxic response and lymphokine production. 303 Nov 70

Five of 22 hemophiliacs who were seropositive for human T cell leukemia virus III (HTLV III) and manifested severe impairment of immune parameters (both in vivo and in vitro) similar to those observed in patients with clinical symptoms of acquired immune deficiency syndrome (AIDS) were chosen for this study. Profound lymphopenia was observed in four of five patients with decreased and qualitatively impaired helper/inducer (T4) cells and increased T suppressor/cytotoxic (T8) cells. Observed in all patients was impaired endogenous production of interleukin-2 (IL-2), expression of the IL-2 receptor combined with diminished responses to mitogens, mixed leukocytes reaction (MLR), and natural killer (NK) reactivity. In vitro supplement of exogenous IL-2 markedly augmented T and NK cell functions, as well as the expression of activation antigens on both T4 and T8 cell in four of five patients. Our findings suggest that a substantial proportion of this cell-mediated immunologic defect in hemophiliacs stems from their inability to produce adequate amounts of IL-2. Interleukin-2 may therefore have the potential for therapy as an immune response modifier in patients with hemophilia by providing beneficial preventive therapy for patients at risk.
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PMID:In vitro restoration by interleukin-2 (IL-2) of the impaired natural killer cell activities, IL-2 receptor expression, and T cell proliferation in hemophilia. 309 Feb 9


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