Cell-mediated immunity to cytomegalovirus (CMV) and herpes simplex virus (HSV) antigens in the acquired immune deficiency syndrome: Interleukin-1 and interleukin-2 modifyin vitro responses

Abstract

Peripheral blood lymphocytes (PBL) were obtained from five patients with the acquired immune deficiency syndrome (AIDS), six homosexual males with lymphadenopathy, and five normal heterosexual controls. Modulation of virus-specific immunity was assayed in vitro by measuring the lymphocyte blastogenic response and the production of lymphokine (leukocyte inhibition factor; LIF) by PBL stimulated with herpes simplex virus (HSV) or cytomegalovirus (CMV) antigens in the presence or absence of interleukin-1 (IL-1) and interleukin-2 (IL-2). PBL from the control and lymphadenopathy subjects responded to both antigens in the lymphocyte transformation assay (LT) measured on day 7, and the responses were significantly enhanced in cultures grown in the presence of antigen and IL-2 (1 U/ml). PBL from the AIDS patients were unresponsive, but responsiveness was restored by the addition of IL-2. The addition of IL-1 (0.02 micrograms/ml) to antigen-stimulated PBL cultures failed to enhance the proliferative responses in all three study groups. LIF production was assayed in the supernatants from day 1 PBL cultures. LIF was not produced by PBL from AIDS patients grown in the presence of viral antigens, whereas three of five patients from the lymphadenopathy group, and three of five control subjects gave rise to positive responses. The addition of IL-1 to the antigen-stimulated cultures enhanced LIF production in the control and lymphadenopathy groups but not in the AIDS patients. The addition of IL-2 did not modulate LIF production by antigen-stimulated PBL from the control or AIDS patients while suppressing the LIF response of the similarly stimulated PBL from the lymphadenopathy patients.

Production of and in vitro response to interleukin 2 in the acquired immunodeficiency syndrome.

“…While interleukin 2 (IL-2), another soluble product (lymphokine) secreted by sensitized T cells (14)(15)(16), does not share IFN-'y's ability to activate macrophages directly (6), it nevertheless has been of considerable interest in AIDS research (17)(18)(19)(20)(21)(22)(23) because of its broad immunoregulatory effects, which include the stimulation and perhaps regulation of IFN--y production (24)(25)(26)(27)(28)(29). Since deficient IL-2 secretion may underlie the failure of AIDS T cells to generate IFN-,y, thereby contributing to susceptibility to various opportunistic infections (2), we examined the capacity of peripheral blood mononuclear cells from patients with both fully established AIDS and its prodrome (AIDS-related complex [ARC]) to produce IL-2 in response to a diverse group of microbial antigens.…”

Lack of Specific Cell Mediated Immunity to Cytomegalovirus in People at Risk for Aids

“…1 (8), and with those of two groups of healthy heterosexuals, one group seropositive and one seronegative for CMV (18). The homosexuals' immunological behavior was similar to that of the CMV infected children, who did not recover from infection, and to that of seronegative controls.…”

“…Alternatively, in our series of patients, the inverted ratio could be attributed to the latent CMV infection, which, as in an HSV 2 infection, can result in persistence of the virus in some peculiar sites (i.e. nervous ganglia), with occasional reactivation of the disease (18).…”

Abnormalities in Host Defense Associated with HIV Infection

“…Peripheral blood T cells from AIDS patients have impaired IL-2 secretion in response to a variety of stimuli 39 . In vitro, recombinant IL-2 can restore some mitogenic responses of AIDS patients’ blood lymphocytes 40 . Clinical trials of IL-2 for HIV infection demonstrate that IL-2 increases CD4+ T cell counts in recipients, without increasing HIV replication, particularly when given intermittently 41 .…”