title: Aspergillus fumigatus extract differentially regulates antigen-specific CD4+ and CD8+ T cell responses to promote host immunity.
abstract: 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-gamma-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.
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: Jianming
authors.initials: J
authors.lastname: Tao
authors.forename: Brahm H
authors.initials: BH
authors.lastname: Segal
authors.forename: Cheryl
authors.initials: C
authors.lastname: Eppolito
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Li
authors.forename: Carly G
authors.initials: CG
authors.lastname: Dennis
authors.forename: Richard
authors.initials: R
authors.lastname: Youn
authors.forename: Protul A
authors.initials: PA
authors.lastname: Shrikant
mesh_terms: D000276:Adjuvants, Immunologic; D019264:Adoptive Transfer; D000818:Animals; D001232:Aspergillus fumigatus / Q000737:chemistry / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002645:Chickens; D007111:Immunity, Cellular / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D010047:Ovalbumin