Regulation of immunity at tissue sites of inflammation.
The acquisition and execution of CD4 effector function are tightly regulated and spatially compartmentalized. In the lymph node (LN), naïve 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.
Sojka
Dorothy K
DK
David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester, NY 14642, USA.
Lazarski
Christopher A
CA
Huang
Yu-Hui
YH
Bromberg
Irina
I
Hughson
Angela
A
Fowell
Deborah J
DJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D018448:Models, Immunological
D016207:Cytokines