Reduction in the Number of Varicella-Zoster Virus-Specific T-Cells in Immunocompromised Children with Varicella

Reduction in the Number of Varicella-Zoster Virus-Specific T-Cells in Immunocompromised Children with Varicella

KENJI MURATA,¹ TAKAYUKI HOSHINA,^1,2 SAGANO ONOYAMA,¹ TAMAMI TANAKA,¹ SHUNSUKE KANNO,¹ MASATAKA ISHIMURA,¹ YUHKI KOGA,¹ HIDEKI NAKAYAMA³ and SHOUICHI OHGA¹

¹Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan
²Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka, Japan
³Department of Pediatrics, National Hospital Organization Fukuoka Higashi Medical Center, Koga, Fukuoka, Japan

Varicella zoster virus (VZV) causes a life-threatening infection in immunocompromised hosts. The immune response to VZV of healthy subjects has been rigorously assessed, but little is known about that of immunocompromised individuals. This study aimed to clarify the primary response to VZV infection in immunocompromised children. This prospective study enrolled six immunocompromised children (median age, 33 months; range, 20-62) receiving steroids or immunosuppressants, and 10 immunocompetent children (median age, 32 months; range, 15-81) with varicella. The immunocompromised children were three patients with acute lymphoblastic leukemia, two recipients with liver transplantation and one patient with juvenile idiopathic arthritis. Interferon-γ-producing CD69⁺T-cells produced by VZV stimulation (VZV-specific T-cells) were studied during the acute or convalescent phase. To further address the direct effect of immunosuppressants, we analyzed the number of VZV-specific T-cells after stimulating peripheral blood mononuclear cells obtained from healthy adults with live-attenuated VZV with or without prednisolone, cyclosporine-A, or tacrolimus. The circulating numbers of lymphocytes in the convalescent stage but not acute stage were lower in immunocompromised children compared with immunocompetent children. In the acute stage, immunocompromised patients showed lower VZV-specific CD8⁺T-cell counts than immunocompetent subjects. In contrast, in the convalescent phase, immunocompromised patients had lower VZV-specific CD4⁺T-cell counts than immunocompetent hosts. The in vitro culture of activated lymphocytes with prednisolone or immunosuppressants significantly decreased the proportion of VZV-specific CD4⁺T-cells. In conclusion, the decreased numbers of VZV-specific CD8⁺T-cells during the acute phase and VZV-specific CD4⁺T-cells during the convalescent phase of disease may account for severe varicella in immunocompromised children.

Keywords —— cellular immunity; chickenpox; immunosuppressive agents; interferon-gamma; varicella-zoster virus

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Tohoku J. Exp. Med., 2020, 250, 181-190

Correspondence: Takayuki Hoshina, M.D., Ph.D., Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807-8555, Japan.

e-mail: hoshina@med.uoeh-u.ac.jp