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Rectification of Age-Associated Deficiency in Cytotoxic T Cell Response to Influenza A Virus by Immunization with Immune Complexes

Biao Zheng^*, Yongxin Zhang, Hongxia He^*, Ekaterina Marinova^*, Kirsten Switzer^*, Daniel Wansley^*, Innocent Mbawuike and Shuhua Han^1,*

^* Department of Immunology, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030

Decline in cellular immunity in aging compromises protection against infectious diseases and leads to the increased susceptibility of the elderly to infection. In particular, Ag-specific cytotoxic T lymphocyte (CTL) response against virus is markedly reduced in an aged immune system. It is of great importance to explore novel strategy in eliciting effective antiviral CTL activity in the elderly. In this study, the efficacy and mechanisms of immunization with immune complexes in overcoming age-associated deficiency in cellular immunity were investigated. In this study, we show that the severely depressed CTL response to influenza A in aged mice can be significantly restored by immunization with immune complexes consisting of influenza A virus and mAb to influenza A nucleoprotein. The main mechanisms underlying this recovery of CTL response induced by immune complex immunization in aged mice are enhanced dendritic cell function and elevated production of IFN- in both CD4⁺ Th1 and CD8⁺ CTLs. Thus, these results demonstrate that immune complex immunization may represent a novel strategy to elicit effective virus-specific cytotoxic response in an aged immune system, and possibly, to overcome age-related immune deficiency in general.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Shuhua Han, Department of Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail address: shan{at}bcm.edu

² Abbreviations used in this paper: HA, hemagglutinin; NA, neuraminidase; NP, nucleoprotein; FcR, Fc receptor; DC, dendritic cell; FDC, follicular DC; IC, immune complex; i.n., intranasally; AFC, Ab-forming cell; BM, bone marrow.

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