Memory CD4⁺ T cells induce innate responses independently of pathogen

 Strutt T, et al. Nature Medicine 16, 558-565 (2010)

Speaker: Alan Hsu (許翊輝)                                                 Time: 14:10~15:00, Oct. 20, 2010

Commentator: Dr. Chrong-Reen Wang (王崇任醫師)         Place: Room 601

Abstract:

        The immune system can recognize microbes directly through pattern recognition receptors (PRRs), which respond to conserved mircobial molecules or motifs called pathogen associated molecular patterns (PAMPs). PRRs rapidly activate intracellular signaling pathways, which can facilitate the production of inflammatory mediators in the innate immune system. Cells that express PRRs include antigen presenting cells (APCs) and other immune cells that are involved in innate immune responses. The APCs are the linker between innate and adaptive immune responses and begin the immunological memory response. Whether adaptive immune cells regulate innate inflammation is largely unknown.

        In this study, the authors measured innate immune related cytokines and chemokines after influenza A virus challenge of naive mice or mice primed with the same virus. They found that memory CD4⁺ T cells could enhance early expression of innate immune related cytokines and chemokines in the lung during influenza virus infection. At the same time showing that CD4⁺ memory T cells could speed up viral clearance. After transfer of T_H1, T_H2, T_H17 or T_H0 memory cells to naive mice followed by infection with influenza virus, the authors found that T_H1 and T_H17 memory T cells recognize antigens by HHC-II⁺ APCs, leading to increased cytokine production and viral control in the initial phase of infection. This protective response was found to be independent of interferon-γ(IFN-γ), tumor necrosis factor-α (TNF-α), and other PAMP recognition pathways. To sum up, this study demonstrates that memory CD4⁺ T cells induce innate inflammatory response independently of traditional pathogen recognition pathways. In addition, the authors showed that activated memory T cells could play a redundant and replacing role with macrophages and dendritic cells to activate other immune responses for pathogen clearance. Finally, this study may help explain why memory CD4⁺ T cells are implied in several autoimmune diseases.

References:

1. Janeway, C.A. Jr. & Medzhitov, R. Innate immune recognition. Annu. Rev. Immunol. 20, 197–216 (2002).

2. Powell, T.J. et al. Priming with cold-adapted influenza A does not prevent infection but elicits long-lived protection against supralethal challenge with heterosubtypic virus. J. Immunol. 178, 1030–1038 (2007).