The organized structure of lymphatic tissues (LTs) constitutes a microenvironment referred to as a niche that plays a critical role in immune system homeostasis by promoting cellular interactions and providing access to cytokines and growth factors on which cells are dependent for survival, proliferation, and differentiation. In chronic human immunodeficiency virus type 1 (HIV-1) infection, immune activation and inflammation result in collagen deposition and disruption of this LT niche. We have previously shown that these fibrotic changes correlate with a reduction in the size of the total population of CD4 ؉ T cells. We now show that this reduction is most substantial within the naïve CD4 ؉ T-cell population and is in proportion to the extent of LT collagen deposition in HIV-1 infection. Thus, the previously documented depletion of naïve CD4؉ T cells in LTs in HIV-1 infection may be a consequence not only of a decreased supply of thymic emigrants or chronic immune activation but also of the decreased ability of those cells to survive in a scarred LT niche. We speculate that LT collagen deposition might therefore limit repopulation of naïve CD4 ؉ T cells with highly active antiretroviral therapy, and thus, additional treatments directed to limiting or reversing inflammatory damage to the LT niche could potentially improve immune reconstitution.

This study evaluated near-infrared spectroscopy (NIRS)-derived measurements in hemodynamically stable patients with severe sepsis, as compared with similar measurements in healthy age-matched volunteers. Prospective, preliminary, observational study in a surgical intensive care unit and clinical research center at a university health center. We enrolled 10 patients with severe sepsis and 9 healthy age-matched volunteers. For patients with severe sepsis, we obtained pulmonary artery catheter and laboratory values three times daily for 3 days and oxygen consumption values via metabolic cart once daily for 3 days. For healthy volunteers, we obtained all noninvasive measurements during a single session. We found lower values in patients with severe sepsis (versus healthy volunteers), in tissue oxygen saturation (StO2), in the StO2 recovery slope, in the tissue hemoglobin index, and in the total tissue hemoglobin increase on venous occlusion. Patients with severe sepsis had longer StO2 recovery times and lower NIRS-derived local oxygen consumption values versus healthy volunteers. In our preliminary study, NIRS provides a noninvasive continuous method to evaluate peripheral tissue oxygen metabolism in hemodynamically stable patients with severe sepsis. Further research is needed to demonstrate whether these values apply to broader populations of patients with systemic inflammatory response syndrome, sepsis, severe sepsis, and septic shock.

The structure of lymphatic tissues is an important component of lymphatic tissue T-cell homeostasis. Collagen deposition in lymphatic tissues (common in HIV infection) disrupts the niche and limits the size of the resident CD4 cell population. In this report we show that a single measurement of lymphatic tissue collagen predicts the magnitude of recovery of the peripheral CD4 cell pool with HAART (P < 0.001). This suggests that collagen-targeted therapies might be of benefit.

Our results suggest that a restrictive transfusion practice is safe for severely head-injured patients.