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

Sahoko Imoto; Maho Suzukawa; Keita Takeda; Isao Asari; Shizuka Watanabe; Shigeto Tohma; Takahide Nagase; Ken Ohta; Katsuji Teruya; Hideaki Nagai

doi:10.1016/j.cyto.2022.155840

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

Cytokine. 2022 May:153:155840. doi: 10.1016/j.cyto.2022.155840. Epub 2022 Mar 8.

Authors

Affiliations

¹ National Hospital Organization Tokyo National Hospital, Tokyo 204-8585, Japan; Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
² National Hospital Organization Tokyo National Hospital, Tokyo 204-8585, Japan. Electronic address: fueta-tky@outlook.jp.
³ National Hospital Organization Tokyo National Hospital, Tokyo 204-8585, Japan.
⁴ Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
⁵ National Hospital Organization Tokyo National Hospital, Tokyo 204-8585, Japan; Japan Anti-Tuberculosis Association, Fukujuji Hospital, Tokyo 193-0834, Japan.
⁶ National Center for Global Health and Medicine, Tokyo 162-8655, Japan.

PMID: 35276635
DOI: 10.1016/j.cyto.2022.155840

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: CD4(+) T cells; CD8(+) T cells; Human immunodeficiency virus-1; Mitogen response; QuantiFERON®-TB.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Blood Cells / metabolism
CD8-Positive T-Lymphocytes / metabolism
Chemokine CCL5
Chemokine CXCL10
Cytokines
HIV Infections*
HIV-1*
Humans
Interleukin 1 Receptor Antagonist Protein
Interleukin-6
Interleukin-8
Mitogens
Tuberculosis*

Substances

Chemokine CCL5
Chemokine CXCL10
Cytokines
Interleukin 1 Receptor Antagonist Protein
Interleukin-6
Interleukin-8
Mitogens