Production of IgG2 Antibodies to Pneumococcal Polysaccharides After Vaccination of Treated HIV Patients May Be Augmented by IL-7Rα Signaling in ICOS+ Circulating T Follicular-Helper Cells

Frontiers in Immunology

Laila N. Abudulai¹  Michael Hunter³  Jeffrey J. Post⁴  Sonia Fernandez⁵  Martyn A. French⁶  Lea-Ann Kirkham⁷  Karli Corscadden⁷ 

[1] Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Perth, WA, Australia;Department of Infectious Diseases, Prince of Wales Hospital, Sydney, NSW, Australia;Department of Infectious Diseases, Royal Victoria Hospital, Belfast, United Kingdom;Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia;School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia;UWA Medical School, The University of Western Australia, Perth, WA, Australia;Wesfarmers Centre for Vaccine and Infectious Disease Research, Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia;

关键词: T follicular cells;    IgG2 antibodies;    pneumococcal 23-polyvalent vaccine;    HIV infection;    IL-7 receptor;   

DOI  :  10.3389/fimmu.2019.00839

来源: DOAJ

【 摘 要 】

Greater understanding of factors influencing the maturation of antibody responses against pneumococcal polysaccharides (PcPs) may improve pneumococcal vaccination strategies. Although PcPs are type 2 T cell-independent antigens thought not to induce follicular immune responses, we have previously shown that IgG2 antibody responses against antigens in the 23-valent unconjugated PcP vaccine (PPV23) are associated with expansion of ICOS+ circulating T follicular helper (cTFH) cells in HIV seronegative subjects but not HIV patients. As IL-7Rα signaling in CD4+ T cells may affect TFH cell function and is adversely affected by HIV-1 infection, we have examined the relationship of IL-7Rα expression on ICOS+ cTFH cells with PcP-specific IgG2 antibody responses. PPV23 vaccination was undertaken in HIV patients receiving antiretroviral therapy (n = 25) and HIV seronegative subjects (n = 20). IL-7Rα expression on ICOS+ and ICOS− cTFH cells was assessed at day(D) 0, 7, and 28. Fold increase between D0 and D28 in serum IgG1 and IgG2 antibodies to PcP serotypes 4, 6B, 9V, and 14 and the frequency of IgG1+ and IgG2+ antibody secreting cells (ASCs) at D7 were also assessed. Decline in IL-7Rα expression on ICOS+ cTFH cells between D0 and D7 occurred in 75% of HIV seronegative subjects and 60% of HIV patients (Group A), with changes in IL-7Rα expression being more pronounced in HIV patients. Group A patients exhibited abnormally high IL-7Rα expression pre-vaccination, an association of serum IgG2, but not IgG1, antibody responses with a decline of IL-7Rα expression on ICOS+ cTFH cells between D0 and D7, and an association of higher IgG2+ ASCs with lower IL-7Rα expression on ICOS+ cTFH cells at D7. As decline of IL-7Rα expression on CD4+ T cells is an indicator of IL-7Rα signaling, our findings suggest that utilization of IL-7 by cTFH cells affects production of IgG2 antibodies to PPV23 antigens in some HIV patients.

【 授权许可】

Unknown