TLR4 and lymphopenia: To investigate the previously unknown mechanisms between HMGB1 and dysregulated immune responses, mainly T cell exhaustion, lymphopenia and dysfunction in PT, we determined whether PT associated HMGB1 levels dictate the onset of early mixed inflammatory responses, including altered cellular expression of RAGE and TLR4 and if neutralization of HMGB1 ameliorates such dysregulated immune responses.