Blockage of regulatory T cells augments induction of protective immune responses by influenza virus-like particles in aged mice

Abstract

Elderly humans over 65 years old are at great risk to pathogenesis by influenza virus infection. However, although influenza vaccines provide effective protection in healthy young adults, protection of elderly adults is substantially lower even with a good match between the vaccine and the circulating influenza virus. To gain insight of the underlying mechanism for the reduced immunogenicity of influenza vaccines in the aged population, we investigated immunogenicity of influenza virus-like particle vaccines in aged mice, which represent a useful model for studying aging associated impairment in immune responses. Specifically, we investigated the effect of inhibiting regulatory T cells in aged mice on induction of protective immune responses by influenza vaccines. Our results showed that injecting anti-CD25 antibodies could down-regulate CD25 on the surface of regulatory T cells and significantly increase the levels of antibody responses induced by VLP immunization in aged mice. Further, the profiles of antibody responses were also changed towards Th1 type by regulatory T cell blockage in aged mice. Moreover, aged mice that were treated by anti-CD25 antibodies prior to vaccination were more effectively protected against lethal influenza virus challenge.

Depletion of CD38‐positive regulatory T cells by anti‐CD38 monoclonal antibodies induces a durable response to SARS‐CoV‐2 vaccination in patients with plasma cell dyscrasia

“…In general, Treg function is activated in the elderly, 14 which reduces the effectiveness of influenza virus and varicella‐zoster virus (VZV) vaccines. 15 , 16 Moreover, the lower number of Tregs are also implicated in autoimmune diseases such as immune thrombocytopenia or transfusion‐related acute lung injury. 17 , 18 However, there are very few reports on the effect of Tregs on COVID‐19 vaccines, as aforementioned.…”

The Complex Role of Regulatory T Cells in Immunity and Aging

“…Along these lines, another study in aged patients showed that non-responder individuals to influenza vaccination have a higher frequency of Treg as well as a higher inflammatory status compared to responders ( 128 ). Depletion of Treg with anti-CD25 treatment prior to influenza infection protected against lethal viral challenge in aged mice ( 129 ). In another study, responders to influenza vaccination showed a higher frequency of Treg compared to non-responders, together with an elevated frequency of early differentiated CD4 + T cells and lower proportion of memory CD4 + cells ( 130 ).…”

Thymic Aging May Be Associated with COVID-19 Pathophysiology in the Elderly

“…If there are too many Treg cells, the antiviral immunity and vaccination efficiency mediated by effector T cells and B cells may be suppressed, resulting in reduced inhibition of viral replication in the elderly; whereas, if Treg cells are insufficient in the inflammatory lung, the excessive immune reaction-induced tissue damage could be detrimental. Utilizing anti-CD25 to block Treg cell function has been demonstrated to augment protective immune responses to influenza virus-like particles in aged mice [ 128 ]. Induced Treg (iTreg) cells can be generated via transforming growth factor- β (TGF-β), while blocking TGF-β signaling impedes the conversion of CD4 T cells into iTreg cells and thereby facilitates immune responses abrogated by Treg suppression [ 129 ].…”