Regulation of immunity at tissue sites of inflammation
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Regulation of immunity at tissue sites of inflammation Dorothy K. Sojka Æ Christopher A. Lazarski Æ Yu-Hui Huang Æ Irina Bromberg Æ Angela Hughson Æ Deborah J. Fowell
Published online: 31 January 2009 Ó Springer Science+Business Media, LLC 2009
Abstract The acquisition and execution of CD4 effector function are tightly regulated and spatially compartmentalized. In the lymph node (LN), naı¨ve CD4? T cells acquire specialized functions by means of expression of distinct cytokines and acquire distinct homing properties. Therefore, both the function and subsequent localization of effector cells appears to be predetermined during differentiation in the LN. Our studies with the protozoa Leishmania major suggest that this centrally (LN) generated effector repertoire can be further edited at the infected tissue site. Cytokine production in the inflamed tissue can be modulated at a number of levels including chemokine-driven differential recruitment of effector cells, the provision of signals for effector cell function and suppression by regulatory T cells (Tregs). The concept that tissue resident pathogens may subvert the centrally generated cytokine repertoire has important therapeutic implications. Novel therapies that focus on manipulating the local infection site to encourage appropriate recruitment or activation of effectors may be particularly beneficial. Keywords CD4 T cell Cytokine Chemokine Inflamed tissue Recruitment Regulatory T cell Leishmania major
Introduction Since the discovery of toll-like receptors (TLRs) in the immune system, our understanding of the crosstalk between pathogen, innate, and adaptive immune cells has grown enormously [1]. Recognition of ‘pathogen-associated molecular patterns’ (PAMPs) by pattern recognition receptors (PRRs), such as the TLRs on innate effectors represents the first step in antimicrobial defense (reviewed in [2–4]). PRR triggering on innate immune cells, including dendritic cells (DC), at the infected tissue site leads to changes in their functional D. K. Sojka C. A. Lazarski Y.-H. Huang I. Bromberg A. Hughson D. J. Fowell (&) David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester, 601 Elmwood Avenue, P.O. Box 609, Rochester, NY 14642, USA e-mail: [email protected]
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Immunol Res (2009) 45:239–250
properties that reflect the specific type of pathogen encounter. The modified DC then convey details about the pathogen in the tissue to the adaptive immune response in the draining lymph node (LN). Following these pathogen-specific cues, naı¨ve T cells differentiate into cytokine producing effector cells expressing a restricted cytokine repertoire. Primed effector T cells then home back to the infected tissue, guided by adhesion and chemokine cues emanating from the pathogen–host interaction in the infected tissue [5], to release cytokines that can be directly antimicrobial or that recruit other immune effectors for pathogen elimi
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