Hobit controls tissue residency of memory T cells

Tissue resident memory T cells, T_RM, represent newly recognized T cell population that play physiologically-relevant role in body's defense against reinfection. T_RM cells are local tissue surveyors and act as a first-line defense [alongside of innate immunity] against tissue invading pathogens. Beyond these information nothing much was known about T_RM cells.

Now, a new paper published in Science showed that transcription factor named Hobit is a master regulator of T_RM cell development.   

Using mouse HSV-1 model, the authors found that by day 30 post-infection, Hobit was selectively up-regulated in T_RM cells recovered from peripheral tissues, such as skin, but not in central lymphoid tissues such as spleen.

Using Hobit-KO T cells the authors were able to confirm that Hobit was indeed intimately involved in development of tissue-resident memory T_RM cells (memory stage, day 40+). Deficiency of another transcription factor, Blimp1, had an additive effect on T_RM cells formation when combined with Hobit deficiency. 

Interesting, Hobit, in combination with Blimp1, also controlled tissue residency of innate cells such NK and NKT cells.

In summary, this study revealed that transcription factor Hobit controls tissue residency of memory T cells, T_RM cells. These data should be considered in developing T cell-oriented vaccines, including cancer immunotherapy (one limitation of this study is that for some reason the authors failed to show actual virus protection data with the regard of Hobit or Hobit + Blimp1 DKO T cells. ).

David Usharauli 

blind love: neuro-immune chemistry

Immune and nervous systems share two unique characteristics: (a) both systems undergo adaptive “education” to discriminate between self and nonself signals and (b) both systems have “memory” to it.

So far few research papers had been published that addressed the question how these two complex systems interact with each other. For example, one paper claimed that T cells can promote neuronal re-generation and hence contribute to the learning process (1). These study was based on evidence that T cell transfer into immunodeficient mice improved neuronal generation. In my opinion, this interpretation fails to take into account the fact that T cell transfer into immunodeficient mice affect not just brain function but for instance, gut permeability too. Why is it important? It is well known that endotoxin (LPS) level in the blood affects brain function. LPS level in the blood, in turn, is influenced by gut permeability, that in turn, is influenced by immune system status. T cell transfer into immunodeficient mice would allow differentiation of gut-homing T cells that may have reduced gut permeability thus indirectly affecting brain function.

If you are interested in neuro-immune research, then I will recommend to read the following two papers recently published in Science (2, 3).

1^st paper from Kevin Tracey's Lab provided the direct evidence that the presence of specialized, acetylcholine-secreting memory T cells were necessary and sufficient to relay signals from nervous system to the immune (2).

2^nd paper from Paul Kubes Lab showed that CD1d-deficient mice (that lack all NKT cells) were more susceptible to stroke-associated immunosuppression compared to wild-type mice (3). This immunosuppression could be prevented by stimulating NKT cells or blocking noradrenalin signaling in these cells because this protective effect of noradrenalin blockade was abolished in CD1d-deficient mice. It is of note that both NKT presence and simultaneous blockade of noradrenalin signaling in these cells was necessary for full protection. This is a kind of paradox. However, because there are two types of NKT cells in mice, there may be a simple explanation. So it will be interesting to compare CD1d-deficient mice to Jalpha18-deficient mice that lack only one type of NKT cells. In my opinion, NKT cells transfer into CD1d-deficient mice would have provided more direct evidence of protective role of this innate NKT cells.

David Usharauli

(1) http://www.nature.com/neuro/journal/v9/n2/full/nn1629.html

(2) http://www.sciencemag.org/content/early/2011/09/14/science.1209985.abstract

(3) http://www.sciencemag.org/content/early/2011/09/14/science.1210301.abstract