title: A T2 cytokine environment may not limit T1 responses in human immunodeficiency virus patients with a favourable response to antiretroviral therapy.
abstract: Low-level production of interferon-gamma (IFN-gamma) marks human immunodeficiency virus (HIV)-induced immunodeficiency and has been ascribed to a bias towards T2 cytokines. This was investigated in two cross-sectional studies of HIV patients who were immunodeficient when they began antiretroviral therapy (ART) and had stable increases in CD4 T-cell counts. Blood leucocytes were assessed unstimulated or after stimulation with cytomegalovirus (CMV), anti-CD3 or mitogen. IFN-gamma and interleukin (IL)-5 responses were initially assessed by enzyme-linked immunosorbent spot-forming cell assay (ELISPOT) and enzyme-linked immunosorbent assay (ELISA). We then adopted a sensitive reverse transcription-polymerase chain reaction (RT-PCR) system to assess IFN-gamma, IL-5, IL-4 and IL-4delta2 (an inhibitory splice variant of IL-4) mRNA. The results were correlated with putative serological markers of a T1 [lymphocyte activation gene-3 (LAG-3), CD26] or a T2 [CD30, immunoglobulin E (IgE)] cytokine environment. IL-5 production and IgE levels were elevated in patients. IgE levels did not correlate with IFN-gamma, but showed an inverse correlation with IL-5 released in culture (P = 0.05). The levels of IL-4, IFN-gamma, IL-5 and IL-4delta2 mRNA were correlated after anti-CD3 stimulation, where IL-5 was the best predictor of IFN-gamma mRNA (P = 0.006). Weak positive correlations were evident between CD30 and cytokine mRNA levels, whilst IgE correlated inversely with IL-4, IL-4delta2, IL-5 and IFN-gamma mRNA levels. These analyses provide no evidence for an inverse relationship between T1 and T2 cytokine responses in HIV patients, but suggest that the elevation of IgE marks low cytokine responses.
authors.affiliation: School of Surgery and Pathology, University of Western Australia, Australia. pprice@cyllene.uwa.edu.au
authors.forename: Patricia
authors.initials: P
authors.lastname: Price
authors.forename: Niamh M
authors.initials: NM
authors.lastname: Keane
authors.forename: Silvia
authors.initials: S
authors.lastname: Lee
authors.forename: Andrew F Y
authors.initials: AF
authors.lastname: Lim
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: McKinnon
authors.forename: Martyn A
authors.initials: MA
authors.lastname: French
mesh_terms: D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D017252:CD3 Complex / Q000494:pharmacology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood*; D003587:Cytomegalovirus / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D015847:Interleukin-4 / Q000097:blood / Q000235:genetics; D015848:Interleukin-5 / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents; D015415:Biomarkers; D017252:CD3 Complex; D016207:Cytokines; D015848:Interleukin-5; D008934:Mitogens; D012333:RNA, Messenger; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma