CD4⁺ T Cell‐Released Extracellular Vesicles Potentiate the Efficacy of the HBsAg Vaccine by Enhancing B Cell Responses

Abstract

T cells secrete bioactive extracellular vesicles (EVs), but the potential biological effects of CD4+ T cell EVs are not clear. The main purpose of this study is to investigate the effects of CD4+ T cell–derived EVs on B cell responses and examine their role in antigen‐mediated humoral immune responses. In this study, CD4+ T cell EVs are purified from activated CD4+ T cells in vitro. After immunization with the Hepatitis B surface antigen (HBsAg) vaccine, CD4+ T cell EVs‐treated mice show stronger humoral immune responses, which is indicated by a greater Hepatitis B surface antibody (HBsAb) level in serum and a greater proportion of plasma cells in bone marrow. In addition, it is found that EVs released from activated CD4+ T cells play an important role in B cell responses in vitro, which significantly promote B cell activation, proliferation, and antibody production. Interestingly, antigen‐specific CD4+ T cell EVs are found to be more efficient than control EVs in enhancing B cell responses. Furthermore, it is shown that CD40 ligand (CD40L) is involved in CD4+ T cell EVs‐mediated B cell responses. Overall, the results have demonstrated that CD4+ T cell EVs enhance B cell responses and serve as a novel immunomodulator to promote antigen‐specific humoral immune responses.

Exosomes in Hepatitis B Virus Transmission and Related Immune Response

“…These results provide us with a new perspective on engineering exosomes to activate the host immune response or directly induce HBV repression. In addition, exosomes released from active CD4+ T cells can promote B cell activation and further enhance the efficiency of the HBsAg vaccine (Lu et al 2019). In a separate study, researchers found that exosomes combined with hepatitis B recombinant antigen induced a humoral immune response similar to the response to HBsAg solution in mice (Jesus et al 2018).…”

Exosome: A New Player in Translational Nanomedicine

“…On the other hand, exosomes derived from the more antigen-specific subtype CD8 + T cell show antiviral activity associated with membrane proteins secreted via exosomes [142]. Moreover, CD4 + -associated exosomes have been reported to significantly boost B cell activation, proliferation and, thus, antibody production [143,144] and to act as immunoregulators [145]. Exosomes secreted by CD4 + CD25 + Foxp3 Treg cells, a subset of CD4 + T cells, specializing in immune tolerance establishment and maintenance, which use a diverse set of mechanisms to enforce peripheral tolerance, are thought to be deeply involved in immune regulation [146].…”

Extracellular vesicles in Inflammatory Skin Disorders: from Pathophysiology to Treatment

“…Increasing evidence has suggested that EVs also participated in T-B cognate interactions. T cell-EVs or their delivered miRNAs/lipids regulated B cell survival, proliferation, and antibody production 4 , 53 , 58 , suggesting that T cell-EVs could be engineered to treat B cell overactivation-related diseases.…”