Abstract
BackgroundCell-mediated immunity plays a crucial role in resistance to intracellular infection. We previously reported antibodies against interferon-gamma (IFN-γ) in HIV− negative (HIV−) patients with acquired immunodeficiency presenting with repeated episodes of disseminated infection caused by uncommon opportunistic intracellular fungal, bacterial, and viral pathogens. This follow-up study aimed to investigate cellular immune responses in these unusual patients.MethodsTwenty HIV− patients presenting with ≥2 episodes of culture- or histopathologic-proven opportunistic infections were enrolled along with age- and sex-matched controls comprised of 20 HIV+ patients plus 20 healthy adults. Monocyte phenotyping and intracellular cytokine production were determined by staining with specific antibodies followed by flow cytometry. Anti-interferon-γ antibodies were measured by enzyme-linked immunosorbent assay, and inducible nitric oxide synthase by reverse-transcription polymerase chain reaction.ResultsThere were no differences among cases, HIV+, and healthy controls in the percentage of monocytes, or CD68 and HLA-DR expression on their surfaces. FcR1 (CD119) expression on monocytes was significantly higher in cases than in HIV+ (p<0.05) and healthy controls (p<0.01), suggesting the presence of activated monocytes in the circulation. Interleukin (IL)-2 and tumor necrosis factor (TNF)-α production in CD4 cells were significantly lower in cases than in healthy controls (p<0.01 and p<0.001, respectively). CD8 production of TNF-α among cases was significantly lower than that of healthy controls (p<0.05).ConclusionImmunodeficiency in HIV− individuals with repeated infections with intracellular pathogens may be associated with one or more of the abnormal immune responses reflected by the reduced production of both IL-2 by CD4 T cells and TNF-α by CD4 T cells and CD8 T cells, as well as presence of anti-IFN-γ antibody, as previously reported.
Highlights
Cell-mediated immunity (CMI) plays a crucial role in resistance to intracellular infection [1,2]
IFN-c acts in synergy with tumor necrosis factor (TNF)-a to enhance expression of the major histocompatibility complex (MHC) and co-stimulatory molecules, and to activate microbicidal substances such as reactive oxygen species, nitric oxide, and lysosomal enzymes of macrophages
Monocyte characteristics We found no differences in the percentages of monocytes identified by expression of CD14 among cases, human immunodeficiency virus type 1 (HIV)-infected controls, nor healthy controls (Fig. 1D)
Summary
Cell-mediated immunity (CMI) plays a crucial role in resistance to intracellular infection [1,2]. Activation of phagocytes, mainly macrophages and dendritic cells, results in the production of interleukin (IL)-12 and tumor necrosis factor (TNF)-a. Cell-mediated immunity plays a crucial role in resistance to intracellular infection. We previously reported antibodies against interferon-gamma (IFN-c) in HIV2 negative (HIV2) patients with acquired immunodeficiency presenting with repeated episodes of disseminated infection caused by uncommon opportunistic intracellular fungal, bacterial, and viral pathogens. This follow-up study aimed to investigate cellular immune responses in these unusual patients
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