Selective defects in cytomegalovirus- and mitogen-induced lymphocyte proliferation and interferon release in patients with acquired immunodeficiency syndrome.

To examine the defect in cellular immunity in patients with acquired immunodeficiency syndrome (AIDS), we studied in vitro lymphocyte proliferation and interferon (IFN) release in response to cytomegalovirus (CMV) antigen and Concanavalin A mitogen in 40 homosexual men with AIDS, 10 homosexual men with chronic lymphadenopathy syndrome, 7 healthy homosexual men, and 18 healthy heterosexual subjects of either sex. CMV serology by an enzyme-linked immunosorbent assay and viral cultures for CMV were performed. Lymphocytes of patients with AIDS showed impaired CMV-specific release of IFN but normal mitogen-induced IFN release.

Interferon-induced 2'-5' oligoadenylate synthetase during interferon-alpha therapy in homosexual men with Kaposi's sarcoma: marked deficiency in biochemical response to interferon in patients with acquired immunodeficiency syndrome.

Titers of circulating interferon (IFN) and the activity of 2'-5' oligoadenylate (2-5A) synthetase, an enzyme specifically induced by IFN, were measured in 28 homosexual men with acquired immunodeficiency syndrome (AIDS) who received one- to six-month courses of antineoplastic therapy with IFN-alpha and in homosexual and heterosexual controls. Fifteen of the patients and two of seven healthy homosexual men had high endogenous levels of 2-5A synthetase. IFN therapy induced further increases in this enzyme in only 10 of the 28 patients with AIDS.

Viral infections and cell-mediated immunity in immunodeficient homosexual men with Kaposi's sarcoma treated with human lymphoblastoid interferon.

Herpesviral infections and cellular immunity were studied in 19 patients with acquired immunodeficiency syndrome who were treated with human lymphoblastoid interferon for Kaposi's sarcoma. Before treatment, cytomegalovirus (CMV) and Epstein-Barr virus were isolated from 18 of 19 patients and 13 of 14 patients, respectively. Serum levels of interferon were measurable in all cases.

Human lymphoblastoid interferon treatment of Kaposi's sarcoma in the acquired immune deficiency syndrome. Clinical response and prognostic parameters.

Thirty consecutive patients with the acquired immune deficiency syndrome were treated with intramuscular human lymphoblastoid interferon for Kaposi's sarcoma. Patients were divided into three groups receiving 7.5 million units/m2 per day, 15 million units/m2 per day, or 25 million units/m2 per day for 28 days.

Interleukin 2 enhances the natural killer cell activity of acquired immunodeficiency syndrome patients through a gamma-interferon-independent mechanism.

Patients with the acquired immunodeficiency syndrome (AIDS) exhibit a variety of disorders of cellular immunity, including a deficient ability to generate cytotoxic T cells and depressed levels of natural killer (NK) cell activity. Interleukin 2 (IL 2) in vitro can markedly augment these depressed immune functions. Because IL 2 can induce the release of interferon-gamma (IFN-gamma) from normal peripheral blood lymphocytes (PBL), and because IFN-gamma may play a role in the regulation of NK cell activity, this study was performed to determine if the IL 2 enhancement of the NK cell activity of patients with AIDS was an IFN-gamma-dependent effect.

Interleukin 2 therapy in infectious diseases: rationale and prospects.

Clinical trials using interleukin 2 as a therapeutic immunomodulating agent in patients with acquired immunodeficiency syndrome have recently begun. In this article we present data from studies which indicate the ability of interleukin 2 in vitro to augment clinically important cytotoxic immune responses in lymphocytes from these patients. These studies provide both a rationale for the current trials and a model for evaluating the potential for use of interleukin 2 in other infectious diseases.

Decreased circulating large granular lymphocytes associated with depressed natural killer cell activity in renal transplant recipients.

Renal transplant recipients (RTR) receiving prednisone and azathioprine (AZ) frequently have depressed natural killer (NK) cell activity. In humans, NK activity is mediated by the large granular lymphocyte (LGL). To determine the mechanism of depressed NK activity among RTR, we quantitated the NK activity of peripheral blood lymphocytes (PBL) and the percentage of circulating LGL in Giemsa-stained cytocentrifuge preparations of PBL from 20 RTR and 6 healthy volunteers.

Use of interleukin-2 in patients with acquired immunodeficiency syndrome.

Twelve patients with acquired immunodeficiency syndrome were treated with a natural product, highly purified human interleukin-2. Doses ranged from 250 to 250,000 units. No clinical responses were seen.

Comparative virulence and immunogenicity of the Towne strain and a nonattenuated strain of cytomegalovirus.

The Towne strain cytomegalovirus and a low-passage strain, Toledo-1, were compared for virulence and immunogenicity in healthy adult male subjects to determine the suitability of the Towne strain for vaccination. Five seropositive subjects who received the Toledo-1 strain developed infections ranging in severity from laboratory abnormalities to mild mononucleosis syndromes (mean incubation, 4.7 weeks).

Herpesvirus infections in the acquired immune deficiency syndrome.

Herpesvirus infections were studied in persons with or at risk for the acquired immune deficiency syndrome (AIDS). The infections diagnosed were as follows: patients with AIDS, cytomegalovirus (CMV) in 34 of 34, Epstein-Barr virus (EBV) in 33 of 34, herpes simplex viruses (HSV) in eight of 34, and varicella zoster virus in four of 34; patients with chronic lymphadenopathy syndrome, CMV in eight of nine and EBV in nine of nine; in healthy homosexual men, CMV in five of 13 and EBV in seven of eight. Cytomegalovirus infections were frequently related to disease and death.

Interleukin 2 therapy in infectious diseases: rationale and prospects.

Clinical trials using interleukin 2 as a therapeutic immunomodulating agent in patients with acquired immunodeficiency syndrome have recently begun. In this article we present data from studies which indicate the ability of interleukin 2 in vitro to augment clinically important cytotoxic immune responses in lymphocytes from these patients. These studies provide both a rationale for the current trials and a model for evaluating the potential for use of interleukin 2 in other infectious diseases.

HLA-restricted cytotoxic T lymphocytes are an early immune response and important defense mechanism in cytomegalovirus infections.

Eighty-eight bone marrow transplant recipients were studied for development of cytomegalovirus (CMV) infections and associated cytotoxic lymphocyte responses. Sixty-one patients developed CMV infection that was diagnosed by virus isolation (18 patients), fourfold rises in serum antibodies (13), or both (30). Interstitial pneumonitis developed in 27 patients.

Importance of cytotoxic lymphocytes during cytomegalovirus infection in renal transplant recipients.

Thirty renal transplant recipients were studied prospectively to evaluate the relationship of cytomegalovirus-specific cytotoxic lymphocyte responses to clinical outcome during cytomegalovirus infection. Cytomegalovirus infection developed in 20 patients; of these 20, 14 had cytomegalovirus-specific cytotoxic lymphocyte responses whereas six did not. Clinical findings (fever, leukopenia, thrombocytopenia, or elevations in serum transaminase levels) were significantly more frequent among patients without responses than among patients with responses (p less than 0.

Interferon-related leukocyte inclusions in acquired immune deficiency syndrome: localization in T cells.

Blood samples from a series of 12 patients with Kaposi's sarcoma or infectious complications of the acquired immunodeficiency syndrome (AIDS) and from 18 homosexual contacts of AIDS patients were screened for interferon-related tubuloreticular inclusions (TRI) in circulating leukocytes. In the AIDS patients, TRI were detected by transmission electron microscopy in 1.5 to 10% of mononuclear cell sections.

NIH conference. Acquired immunodeficiency syndrome: epidemiologic, clinical, immunologic, and therapeutic considerations.

The acquired immunodeficiency syndrome is a new disease whose cause is unknown but is almost surely due to a transmissible agent, most likely a virus. The disease is clearly spread by sexual contact, particularly homosexual activity. Blood-borne transmission constitutes the other major recognized form of spread of the disease, although it is highly likely that the disease is not readily spread through casual, nonsexual, non-blood-borne routes.

Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome.

We studied B-lymphocyte function in 12 homosexual male patients with the acquired immunodeficiency syndrome, 5 healthy homosexual men, and 12 heterosexual controls. In comparison with the heterosexual controls, the patients were found to have elevated numbers of cells spontaneously secreting immunoglobulin, decreased B-cell proliferative responses to T-cell-independent B-cell mitogens, and qualitatively deficient helper T cells. The hyperactive spontaneous B-cell responses as well as the refractoriness to signals for T-cell-independent B-cell activation were highly suggestive of an in vivo polyclonal activation of B cells and may have been responsible for the manifestations of B-cell hyperreactivity, such as hypergammaglobulinemia, seen in these patients.

Treatment of intraocular inflammatory disease with cyclosporin A.

Eight patients with bilateral sight-threatening posterior uveitis of non-infectious aetiology that had not responded to corticosteroid or cytotoxic therapy were given cyclosporin A. Seven of the eight responded with improvement in visual acuity and disappearance of ocular inflammatory activity. The seven included two with Behçet's disease, who also had improvement in non-ocular symptoms.