Sunday, September 18, 2011

OX40/CD30 lay off Foxp3

 Since it's discovery in 2001, a transcription factor called Foxp3 has been recognized as a master regulator of autoimmune disease. It's total deficiency in CD4 T cells has such a profound effect that mouse that lacks it usually die of inflammatory multi-organ failure within 3 weeks of birth.

We don't know how exactly Foxp3+ CD4 T cells prevent autoimmunity. Currently, there is no mechanistic model that could satisfactorily explain their function. Even at the theory level, Foxp3+ T cell role is either totally ignored/dismissed (for example, in SNS model) or characterized as an immune class-specific effector/memory T cells (for example, in danger model). In short, the viable concept of negative regulation of immune system by antigen-specific Foxp3+ CD4 T cells is yet to come.

If you are interested in Foxp3+ T cell biology, I recommend reading a new study recently published in Journal of Experimental Medicine (1). This study, by Fabrina M. Gaspal and et al, made an interesting observation that mice triple deficient in OX40/CD30/Foxp3 are healthy. It appears that OX40/CD30 pathways control autoimmune potential of self-specific T cells. The simple explanation I favor is that in the absence of OX40/CD30 signaling, effector/memory T cell differentiation is impaired in general and as a consequence, self-specific T cells loose the capability to damage the tissue. Of course, the one caveat of the paper is that we have no idea whether those triple deficient mice are capable of mounting a proper immune response to non-self antigenic challenge or infection. If they cannot, then the absence of autoimmunity is the direct consequence of immunodeficiency (similar to gamma-c receptor deficient mouse model). However, if they could respond to non-self antigenic challenge or infection, then this model has made an unique contribution to our understanding of Foxp3 biology.

David Usharauli

1 comment:

  1. Hi Dude,

    This is the perfect blog for anyone who wants to know about this topic. CD4 T cell help accrued during priming of tumor specific CD8 T cells with a vaccine, as opposed to the benefits delivered by the presence of cognate CD4 cells within the tumor...

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