Mechanisms of T cell plasticity

Continuing with the topic of T helper cell “shapeshifting,” Hirahara et al. report on the complexity of environmental determinants and epigenetic factors that orchestrate T helper cell plastic responses (Journal of Allergy and Clinical Immunology 2013; 131(5):1276-1287). 

The authors discuss the regulatory and metabolic factors that affect the plastic capabilities of helper T cells.  Beginning with an excellent overview of the current taxonomy of Th cells, Hirahara et al. reviews the current understanding of CD4 T cell fate and their homeostatic interactions within T helper cell lineages. 

Further discussion addresses the idea of “signature” transcription factors and cytokine production in T cell lineages.  The authors question the accuracy and usefulness of this static characterization in light of the accumulating knowledge of T helper cell capacity for expression of multiple transcription factors and cross-family cytokines under the influence of different pathological contexts.   The complexity and variable expression of “master” transcription regulators is covered, in particular the STAT family of binding proteins. 

Hirahara et al. go on to discuss the transcription factor “orchestra” that permits the observed plasticity in response to different environmental conditions.  Transcription, epigenetic, and metabolic systems are discussed, with particular elaboration on those elements that are responsible for the accessibility of genes that can be transcribed.  Discussion includes active and silent histone modifiers, methylation, and “enhancers” found in junk DNA that are now being discovered as critical to gene expression. 

The authors conclude noting that future therapeutic approaches could possibly manipulate “good” CD4 T cell phenotypes to persist, while diminishing “bad” phenotypes.  Importantly, they point out that existing technologies may provide the tools necessary to accomplish this, but must be re-evaluated for their impact on factors that promote helper T cell plasticity.