Evaluation of cytokine levels in response to mitogen among HIV-1-infected blood cells and their relationships to the number of T cells

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2022-05, Vol.153, p.155840-155840, Article 155840
• Main Authors: Imoto, Sahoko, Suzukawa, Maho, Takeda, Keita, Asari, Isao, Watanabe, Shizuka, Tohma, Shigeto, Nagase, Takahide, Ohta, Ken, Teruya, Katsuji, Nagai, Hideaki
• Format: Article
• Language: English
• Subjects: Blood Cells - metabolism; CD4+ T cells; CD8+ T cells; CD8-Positive T-Lymphocytes - metabolism; Chemokine CCL5; Chemokine CXCL10; Cytokines; HIV Infections; HIV-1; Human immunodeficiency virus-1; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-6; Interleukin-8; Mitogen response; Mitogens; QuantiFERON®-TB; Tuberculosis
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2022.155840

•We assessed the effect of HIV-1 infection and T cell count on cytokine production.•Mitogen-induced IFN-γ from HIV-1+ cells correlated with CD4+/CD8+ T cell count.•Biomarkers independent of T cell count may be useful for immune-compromised hosts.•Mitogen-induced cytokine synthesis is unique among HIV-1-infected blood cells. Human immunodeficiency virus-1 (HIV-1) infection causes loss and anergy of CD4+ and CD8+ T cells, leading to opportunistic infections, including tuberculosis (TB). QuantiFERON®-TB (QFT) is used as a diagnostic tool to detect TB, but it exhibits limited accuracy among subjects with low CD4+ T cell numbers, including HIV-1-infected individuals. The present study aimed to determine the effect of HIV-1 infection and patients’ blood T cell numbers on cytokine production in response to mitogen (Mit) stimulation. The number of CD4+ and CD8+ T cells in HIV-1-infected individuals was quantified. Levels of various cytokines in Mit-stimulated and un-stimulated (Nil) supernatants of QFT gold “in tube” were assessed using a MAGPIX System. The correlation between cytokine levels and CD4+/CD8+ T cell counts in response to Mit was analyzed. The cytokine levels were compared between HIV-1-infected and healthy subjects. HIV-1-infected individuals (110) and control subjects (27) were enrolled. Interferon (IFN)-γ, interleukin-1 receptor antagonist (IL-1RA), IL-6, IL-8, and regulated on activation, normal T cell expressed and secreted (RANTES) values in Mit-Nil tubes showed a significant correlation with CD4+ T cell counts, while IFN-γ, IL-6, and IFN-γ-induced protein 10 (IP-10) values in Mit-Nil tubes had significant correlation with CD8+ T cell counts. IL-1RA, IL-8, IP-10, platelet-derived growth factor (PDGF)-BB, and RANTES levels in Nil tubes were significantly higher in the HIV-1-infected group. IFN-γ, IL-2, IL-5, IL-6, IP-10, and macrophage inflammatory protein-1β values in Mit-Nil tubes were significantly higher, and PDGF-BB and RANTES levels were significantly lower in the HIV-1-infected group. The functions of HIV-1-infected T cells and uninfected T cells, such as spontaneous and responsive cytokine production in response to Mit, were different. Our findings may be useful for developing new clinical tools for patients with low T cell counts. Additionally, the study provides new insights into the pathogenesis of HIV-1 infection.