Review Article

Positive and Negative Regulation of Cellular Immune Responses in Physiologic Conditions and Diseases

Figure 2

Expression of regulatory molecules following pathogen infection. Schematic overview of the pattern of expression of regulatory molecules. Following pathogen infection, key coinhibitory molecules are upregulated with different kinetics and play a role in regulating the development and the fate of effector T cells. In most cases, pathogens replication is controlled by the immune system leading to the contraction of effector T cells. Many different coinhibitory molecules, that is, PD-1, CTLA-4, BTLA, SLAM, and 2B4, play a role during this process. The remaining memory T cells (which are depending on the current models, derived either directly from naïve cells or from effector cells) express some coinhibitory molecules which depend on the type and biology of the pathogens. A hallmark of memory T cells is the lack of simultaneous expression of multiple coinhibitory molecules. Some regulatory molecules, however, are expressed by memory T cells, and this depends on the type of memory subset, that is, central or effector memory T cells. Conversely, when pathogens replication is not controlled, continuous stimulation of T cells, due to antigen persistence, prevents the full contraction of effector cells and leads to their functional exhaustion. A hallmark of exhausted effector cells is the simultaneous expression of several coinhibitory molecules. The simultaneous expression of these coinhibitory molecules is associated with their functional anergy.
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