Restoration of HIV-Specific Cell-Mediated Immune Responses by Interleukin-12 in Vitro

Abstract

Peripheral blood mononuclear cells (PBMCs) from many asymptomatic individuals infected with human immunodeficiency virus-type 1 (HIV) are unresponsive as measured by in vitro T cell proliferation and interleukin-2 (IL-2) production to influenza virus and synthetic peptides of HIV envelope (Env). Strong influenza virus- and Env-stimulated IL-2 responses and T cell proliferation were restored when cultures were stimulated in the presence of IL-12. Interferon-gamma production by PBMCs from HIV seropositive (HIV+) patients was also restored with IL-12. Furthermore, in vitro antigen-specific production of IL-2 and proliferation of PBMCs from HIV- donors were suppressed by antibody to IL-12, but were not enhanced by addition of exogenous IL-12. Thus, IL-12 may be limiting in PBMCs from HIV+ but not HIV- individuals. These findings demonstrate that IL-12 can restore HIV-specific cell-mediated immunity in vitro in HIV-infected individuals and suggest a potential use of IL-12 in augmenting the diminished immunologic functions associated with HIV infection.

ISCOMs: an adjuvant with multiple functions

“…Lately, the ability of adjuvants to alter the nature of immune responses has received considerable attention. For example, the influence of adjuvants on the pattern of cytokines produced by T helper (Th) cells is of great interest because of the importance of different Th cell subsets for generation of protective immunity against certain infectious diseases [83][84][85]. Several studies in murine models have addressed this issue with regard to ISCOMs.…”

Lymphokine‐Activated Cytotoxicity in Peripheral Blood Mononuclear Cells of Severely Immunocompromised HIV‐Infected Patients

“…It is possible that regimens using different cytokines, such as IL-12 [20], higher concentrations of cytokines, different combinations of cytokines, or longer incubations could result in even higher levels of cytotoxicity in this group of patients. It should be emphasized, however, that there is no current empirical evidence that augmenting NK or ADCC functions in patients with advanced HIV infection will result in clinical benefits.…”

“…For each subject, unactivated and lymphokine-activated specimens were assayed in parallel. Twenty per cent lytic units (LU 20 ) were calculated from the four E:T ratios utilizing software generously provided by Dr Hugh Pross [12].…”

Selective CD4+ T cell deletion after specific activation in HIV-infected individuals; protection by anti-CD28 monoclonal antibodies

“…Restoration of cell-mediated immune responses in vitro was not restricted to anti-CD28 MoAb, as it has recently been shown that IL-12 was also able to restore antigen-specific proliferation of CD4 T cells from HIV-infected individuals [19]. IL-12 also appears to inhibit AICD (G. Shearer, personal communication).…”