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Published online before print June 22, 2006

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(Journal of Leukocyte Biology. 2006;80:529-537.)
© 2006 by Society for Leukocyte Biology

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

Jianming Tao^*, Brahm H. Segal^*,, Cheryl Eppolito^*, Qingsheng Li^*, Carly G. Dennis, Richard Youn and Protul A. Shrikant^*,1

^* Departments of Immunology and
Medicine, Roswell Park Cancer Institute, Buffalo, New York

¹ Correspondence: Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263. E-mail: protul.shrikant{at}roswellpark.org

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--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.

Key Words: rodent • transgenic • cell activation • cell differentiation • cytotoxicity • spleen • lymph nodes • tumor immunity

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