Aspergillus fumigatus extract differentially regulates antigen-specific CD4+ and CD8+ T cell responses to promote host immunity

Journal of Leukocyte Biology

Brahm H. Segal³  Jianming Tao¹  Cheryl Eppolito¹  Protul A. Shrikant¹  Qingsheng Li¹  Carly G. Dennis²  Richard Youn² 

[1] Departments of Immunology and Departments of Immunology and Departments of Immunology and;Medicine, Roswell Park Cancer Institute, Buffalo, New York Medicine, Roswell Park Cancer Institute, Buffalo, New York Medicine, Roswell Park Cancer Institute, Buffalo, New York;Departments of Immunology and Medicine, Roswell Park Cancer Institute, Buffalo, New York Departments of Immunology and Departments of Immunology and Medicine, Roswell Park Cancer Institute, Buffalo, New York Medicine, Roswell Park Cancer Institute, Buffalo, New York Departments of Immunology and Medicine, Roswell Park Cancer Institute, Buffalo, New York

关键词: rodent;    transgenic;    cell activation;    cell differentiation;    cytotoxicity;    spleen;    lymph nodes;    tumor immunity;   

DOI  :  10.1189/jlb.0106026

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Invasive aspergillosis is a major cause of morbidity and mortality in the severely immunocompromised. The paucity of information about the mechanisms by which Aspergillus-derived factors regulate antigen-specific T cell responses in vivo poses a significant hurdle for devising effective immunization strategies to treat or prevent aspergillosis. By monitoring adoptively transferred T cell receptor transgenic, naive CD4+ (OT-II) and CD8+ (OT-I) T cells specific for distinct peptides of a nominal antigen, chicken ovalbumin (OVA), we demonstrate that sensitization with Aspergillus fumigatus (Af) extract plus OVA protein considerably enhances OT-I and OT-II T cell activation, which results in clonal expansion, primarily as a result of increased proliferation. The sensitization provided by Af extract promotes OT-I expansion accompanied by differentiation into interferon-γ-producing cytotoxic cells. It is surprising that no effector differentiation of the induced OT-II response was observed. Moreover, the Af extract-induced OT-I and OT-II T cell expansion was transient, as considerable contraction in the numbers of detectable OT-I and OT-II T cells was evidenced by Day 10. In agreement with these observations, sensitization with Af extract plus OVA marginally promoted host immunity against an OVA-expressing thymoma (E.G7) challenge, and the protection was enhanced by resensitization with Af extract and OVA. Our results demonstrate the ability of Af extract to differentially regulate antigen-specific CD4+ and CD8+ T cell responses, resulting in limited augmentation of host immunity. This information suggests that strategies to target CD4+ T cell effector maturation may promote host immunity to Aspergillus and unexpectedly demonstrates the use for Af extract as a CD8+ T cell adjuvant.

【 授权许可】

Unknown