Abstract
Inflammatory reactions are believed to be triggered by innate signals and have a major protective role by recruiting innate immunity cells, favoring lymphocyte activation and differentiation, and thus contributing to the sequestration and elimination of the injurious stimuli. Although certain lymphocyte types such as TH17 cells co-participate in inflammatory reactions, their generation from the naïve pool requires the pre-existence of an inflammatory milieu. In this context, inflammation is always regarded as beginning with an innate response that may be eventually perpetuated and amplified by certain lymphocyte types. In contrast, we here show that even in sterile immunizations or in MyD88-deficient mice, CD8 T cells produce a burst of pro-inflammatory cytokines and chemokines. These functions follow opposite rules to the classic CD8 effector functions since they are generated prior to cell expansion and decline before antigen elimination. As few as 56 CD8+ inflammatory effector cells in a lymph node can mobilize 107 cells in 24 h, including lymphocytes, natural killer cells, and several accessory cell types involved in inflammatory reactions. Thus, although inflammation modulates cognate responses, CD8 cognate responses also initiate local inflammatory reactions.
Highlights
The main CD8 effector functions are believed to be the production of IFN-γ and cytotoxic activity (CTL), which are induced after extensive division
These stable interactions would lead to T cell activation and the subsequent down-regulation of the sphingosine-1-phosphate (S1P) receptor S1P1 at the T cell surface, preventing antigenspecific T cells to egress the lymphoid organ [6]
CD8+ INFLAMMATORY EFFECTOR T CELLS DO NOT FOLLOW THE RULES THOUGHT TO GOVERN CD8+ DIFFERENTIATION INTO EFFECTOR CELLS Since in the first 1–4 days after antigen administration cell input to the DLN is much increased, we studied if CD8 T cells would express mediators justifying this increase
Summary
The main CD8 effector functions are believed to be the production of IFN-γ and cytotoxic activity (CTL), which are induced after extensive division. It was shown that CD69 expression induced the down-regulation of S1P1 since cells from CD69− mice failed to be retained [7, 8] These events only explain why antigen-specific-cells remain in contact with the APCs presenting the antigen. They do not explain how all lymphocytes dispersed throughout the body are “screened” for such binding capacity during a very short time-period after immunization. This is problematic since it was shown that immediately after infection the number of APCs is very low: using the dose L50 of influenza virus in aerosols only four infectious particles were transmitted [9]. Some circulating antigen-specific-cells may fail to contact these rare APCs, unless their transit time through the draining lymph node (DLNs) is considerably modified
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