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Hepatitis C virus (HCV) has been reported to elicit B and T cell immunity in infected patients. Despite the presence of antiviral immunity, many patients develop chronic infections leading to cirrhosis, hepatocellular carcinoma, and liver failure that can require transplantation. We have previously described the presence of HLA-A2-restricted, HCV NS3-reactive cytotoxic T lymphocytes (CTL) in the blood of HLA-A2 ؊ liver transplantation patients that received an HLA-A2 ؉ liver allograft. These T cells are analogous to the "allospecific" T cells

The CD8 coreceptor on T cells has two functions. Namely, CD8 acts to stabilize the binding of the T-cell receptor (TCR) to the peptide-MHC complex while localizing p56 lck (lck) to the TCR/CD3 complex to facilitate early signaling events. Although both functions may be critical for efficient activation of a CTL, little is known about how the structural versus signaling roles of CD8, together with the relative strength of the TCR, influences T-cell function. We have addressed these issues by introducing full-length and truncated versions of the CD8A and CD8B chains into CD8 À Jurkat cell clones expressing cloned TCRs with known antigen specificity and relative affinities. Using a combination of antigen recognition and tetramer-binding assays, we find that the intracellular lck-binding domain of CD8 is critical for enhanced T-cell activation regardless of the relative strength of the TCR. In contrast, the extracellular domain of CD8 seems to be critical for TCRs with lower affinity but not those with higher affinity. Based on our results, we conclude that there are different requirements for CD8 to enhance T-cell function depending on the strength of its TCR. (Cancer Res 2006; 66(23): 11455-61)

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BACKGROUND AND PURPOSE:Ischemic stroke is commonly embolic, either from carotid atherosclerosis or from cardiac origin. These potential sources of emboli need to be investigated to accurately prescribe secondary stroke prevention. Moreover, the mortality in ischemic stroke patients due to ischemic heart disease is greater than that of age-matched controls, thus making evaluation for coronary artery disease important in this patient population. The purpose of this study was to evaluate the image quality of a comprehensive CTA protocol in patients with acute stroke that expands the standard CTA coverage to include all 4 chambers of the heart and the coronary arteries.

Effective immunotherapy using T cell receptor (TCR) gene-modified T cells requires an understanding of the relationship between TCR affinity and functional avidity of T cells. In this study, we evaluate the relative affinity of two TCRs isolated from HLA-A2-restricted, gp100-reactive T cell clones with extremely high functional avidity. Furthermore, one of these T cell clones, was CD4 -CD8 -indicating that antigen recognition by this clone was CD8 independent. However, when these TCRs were expressed in CD8 -Jurkat cells, the resulting Jurkat cells recognized gp100:209-217 peptide loaded T2 cells and had high functional avidity, but could not recognize HLA-A2 + melanoma cells expressing gp100. Tumor cell recognition by Jurkat cells expressing these TCRs could not be induced by exogenously loading the tumor cells with the native gp100:209-217 peptide. These results indicate that functional avidity of a T cell does not necessarily correlate with TCR affinity and CD8-independent antigen recognition by a T cell does not always mean its TCR will transfer CD8-independence to other effector cells. The implications of these findings are that T cells can modulate their functional avidity independent of the affinity of their TCRs.

No abstract

Superficial venous insufficiency is a common problem associated with varicose veins. Venous insufficiency and varicose veins can be symptomatic, but more commonly they are a cosmetic concern. In this article, we discuss the relevant anatomy and pathophysiology of superficial venous insufficiency, review the current literature for varicose vein treatment, and cover the technical aspects of diagnosing and treating superficial venous insufficiency. Saphenofemoral junction incompetence with resultant greater saphenous vein reflux is the most common cause of varicose veins; because this condition constitutes the majority of patients encountered in practice, we will concentrate on this area. Endovenous laser ablation and sclerotherapy are covered, including patient workup and selection, procedure set-up, and anesthesia.