title: Cellular immune responses in HIV-negative immunodeficiency with anti-interferon-γ antibodies and opportunistic intracellular microorganisms.
abstract: BACKGROUND
  Cell-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.
  
  
  METHODS
  Twenty 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.
  
  
  RESULTS
  There 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).
  
  
  CONCLUSIONS
  Immunodeficiency 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.
authors.affiliation: Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Jiraprapa
authors.initials: J
authors.lastname: Wipasa
authors.affiliation: Department of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Panuwat
authors.initials: P
authors.lastname: Wongkulab
authors.affiliation: Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Kriangkrai
authors.initials: K
authors.lastname: Chawansuntati
authors.affiliation: Department of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Romanee
authors.initials: R
authors.lastname: Chaiwarit
authors.affiliation: Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand; Department of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Khuanchai
authors.initials: K
authors.lastname: Supparatpinyo
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D018023:HIV Seronegativity / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology*; D042541:Intracellular Space / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D000906:Antibodies; D016207:Cytokines; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II