Naive T cell circulation is restricted to secondary lymphoid organs. Effector and memory T cells, in contrast, acquire the ability to migrate to nonlymphoid tissues. In this study we examined whether nonlymphoid tissues contribute to the differentiation of effector T cells to memory cells and the long-term maintenance of memory T cells. We found that CD4, but not CD8, effector T cell differentiation to memory cells is impaired in adoptive hosts that lack secondary lymphoid organs. In contrast, established CD4 and CD8 memory T cells underwent basal homeostatic proliferation in the liver, lungs, and bone marrow, were maintained long-term, and functioned in the absence of secondary lymphoid organs. CD8 memory T cells found in nonlymphoid tissues expressed both central and effector memory phenotypes, whereas CD4 memory T cells displayed predominantly an effector memory phenotype. These findings indicate that secondary lymphoid organs are not necessary for the maintenance and function of memory T cell populations, whereas the optimal differentiation of CD4 effectors to memory T cells is dependent on these organs. The ability of memory T cells to persist and respond to foreign Ag independently of secondary lymphoid tissues supports the existence of nonlymphoid memory T cell pools that provide essential immune surveillance in the periphery.

The mechanism of skin allograft rejection has been thought to require presentation of graft antigen by resident epidermal Langerhans cells (LCs). We have previously engineered mice that have a selective and constitutive absence of epidermal LCs. By using donor skin from these LC-deficient mice, we show that LCs are not required for rejection of major (FVB --> B6) or minor (H-Y, male --> female on B6 background) antigen-mismatched skin grafts. On the FVB background, where H-Y mismatched grafts are normally maintained indefinitely, grafts lacking LCs are efficiently rejected. Thus, LCs in the donor graft are required for long-term skin engraftment, which supports a regulatory role for LCs in skin graft acceptance.

Toll-like receptors (TLR) are critical sentinels of the host innate immune system. Prior evidence has clearly demonstrated that these receptors are essential to immune recognition of invading pathogens. However, there is emerging evidence that TLR signaling participates in inflammation that is not driven by microorganisms. In the setting of solid organ transplantation, there is accumulating evidence, both in experimental and clinical studies, that TLR signaling is involved in the immune recognition of allografts. Further investigation of how innate immunity impacts solid organ transplantation will likely lead to improved therapeutics for transplant recipients.

Background: It is a common clinical impression that fatigue is a frequent, and often debilitating, symptom in patients with chronic hepatitis C virus (HCV) infection. However, despite its obvious clinical importance, several aspects of fatigue, including its relationship with the underlying liver disease and the presence of psychologic disturbances, have not been well examined. Goals: The current study was carried out to assess these issues. Study: A total of 149 subjects were included in the study and were assigned to one of the following study groups: healthy controls (31), chronic HCV infection (24), combined HCV infection and chronic alcohol abuse (32), alcoholic liver disease (22), and chronic non-liver diseases (40). All subjects were administered investigator-assisted questionnaires designed to analyze the presence and severity of fatigue and psychologic abnormalities. Results: The mean (±SD) fatigue scores in patients with chronic HCV infection (140 ± 22.9; p ‫ס‬ 0.002), alcoholic liver disease (127 ± 31.4; p < 0.001), mixed (HCV/alcoholic) liver disease (131 ± 29.0; p < 0.001), and chronic non-liver diseases (128 ± 35.9; p ‫ס‬ 0.004) were significantly greater compared to with healthy subjects (101 ± 31.8). The total fatigue scores were higher in HCV-infected subjects compared with the other patient groups, but the differences failed to reach statistical significance. Moreover, the fatigue experienced by patients with HCV did not improve with rest as effectively as in the other study groups. All patient groups had higher scores for psychologic disturbances compared with healthy subjects. Conclusions: The current study shows that fatigue and psychologic disturbances occur frequently in chronic diseases. The fatigue experienced by patients with HCV infection is more severe and intransigent and responds poorly to relieving factors. Moreover, patients with HCV infection are more depressed and harbor greater feelings of anger and hostility compared with those with non-liver chronic diseases. These observations are important because proper management of the psychologic symptoms may have a favorable impact on the quality of life of patients with HCV infection.