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Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT). Donor T cells are key mediators in pathogenesis, but a contribution from host T cells has not been explored, as conditioning regimens are believed to deplete host T cells. To evaluate a potential role for host T cells in GVHD, the origin of skin and blood T cells was assessed prospectively in patients after HSCT in the absence of GVHD. While blood contained primarily donor-derived T cells, most T cells in the skin were host derived. We next examined patient skin, colon, and blood during acute GVHD. Host T cells were present in all skin and colon acute GVHD specimens studied, yet were largely absent in blood. We observed acute skin GVHD in the presence of 100% host T cells. Analysis demonstrated that a subset of host T cells in peripheral tissues were proliferating ([Ki67.sup.+]) and producing the proinflammatory cytokines IFN-[gamma] and IL-17 in situ. Comparatively, the majority of antigen-presenting cells (APCs) in tissue in acute GVHD were donor derived, and donor-derived APCs were observed directly adjacent to host T cells. A humanized mouse model demonstrated that host skin-resident T cells could be activated by donor monocytes to generate a GVHD-like dermatitis. Thus, host tissue-resident T cells may play a previously unappreciated pathogenic role in acute GVHD., Introduction Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT) (1-6). Current dogma holds that donor T cells, either transferred with or [...]

Kidney transplants appear to substantially improve survival rates in people with end-stage kidney disease. Researchers compared mortality rates among 228,552 dialysis patients, some of whom were on a waiting list for a transplant or who had received a kidney transplant. Those on the waiting list had much lower mortality rates than those who were not. This indicates that healthier patients are placed on the waiting list. However, compared to those still on the waiting list, those who got a kidney transplant still had much lower mortality rates in the long-term.

There are several reasons why a kidney transplant can fail independently of an antigen mismatch. Researchers followed 31,515 people who received a kidney transplant for five years. During the study, 5,883 patients had to begin dialysis because their transplant failed, 2,404 died with a failed transplant and 2,041 died with a functioning kidney. Young patients were more likely to have a graft failure, as were those with large body surface area. The age of the donor also contributed, with donors between 15 and 34 offering the best chance of a functioning graft., Objective.--To determine the association of various antigen-independent factors with long-term cadaveric kidney transplant failure. Design.--Cohort analytic study. Setting.--Kidney transplant centers (N=131) in the United States. Patients.--A total of 31 515 patients who received cadaveric kidney transplants between October 1987 and December 1991. Patients with unknown or uninterpretable vital status or graft survival time (n=264 [0.8%]) were excluded. Main Outcome Measure.--Graft failure, estimated at 2 extremes, depending on whether the death of a patient with a functioning graff was censored ("censored graff failure") or not ("uncensored graft failure"). Results.--During the 62-month study period, 5883 patients required the reinstitution of dialysis because of graff failure, 2404 patients died with graff failure, and 2041 patients died with a functioning graft. The relative risks of censored and uncensored graft failure were significantly associated with donor age, sex, and race and recipient body surface area, after adjusting for recipient age, sex, race, diabetes, cold ischemia time, panel cross-reactivity, pretransplant blood transfusions, previous renal transplantation, functional status, and HLA antigert mismatch. Conclusions.--In cadaveric kidney transplantation, selected demographic and anthropometric factors are significantly related to long-term graft outcomes, even after adjusting for well-known antigen-dependent risk factors. These results support the hypothesis that the supply of viable donor nephrons and the physiologic demands of the transplant recipient are important determinants of long-term graff failure. Antigen-independent factors such as donor age should be incorporated into organ allocation algorithms to optimize equity and efficiency. JAMA. 1996;276:1732-1736

Patients who receive transplanted organs from donors who are infected with the hepatitis C virus (HCV) are likely to develop liver disease. Research indicates that organ transplantation can transmit infectious diseases such as hepatitis. A study of organ recipients shows that transmission approaches 100% when donors are infected. Using a polymerase chain reaction test to detect the HCV RNA that indicates an active infection, it was discovered that all 13 recipients of organs from infected donors tested positive for HCV RNA after transplantation, although all tested negative before their transplants. A group of 11 donors was tested for HCV RNA after they had donated organs. Nine of the 11 tested positive. Eventually 23 of 24 recipients of organs from these donors tested positive for HCV. This is a 96% rate, compared to the 27% rate of a group of recipients tested before transplantation. When both donors and recipients tested negative for HCV RNA before the transplantation, no cases of hepatitis infection were detected after the transplants.

Between 7 percent and 24 percent of the patients who undergo kidney transplantation develop liver disease; in most cases, the cause of the disease is not identified. To determine whether infection with hepatitis C virus (HCV) could be the cause of liver disease following transplantation, tests were carried out on blood samples taken from all 716 organ donors to the New England Organ Bank during the past five years, and on the 29 recipients of their organs. The blood samples were analyzed for the presence of antibodies against HCV (anti-HCV) and hepatitis B. In addition, clinical information concerning the donors' health was reviewed. Results showed that 13 of the donors (1.8 percent) tested positive for anti-HCV; organs from 12 of these donors were actually used. No donor had clinical signs of hepatitis. Twenty-nine organs (19 kidneys, 6 hearts, 4 livers) were transplanted into recipients. Seven of 26 recipients, for whom blood tests were performed prior to transplantation, tested positive for anti-HCV. After transplantation, non-A, non-B hepatitis developed in 14 organ recipients (48 percent). The disease developed with the same prevalence in all recipients, regardless of the organ they had received, beginning, on average, 3.8 months after transplantation. Two patients died as a result of liver failure and the other 12 developed chronic liver disease. Analyses of the blood samples for 13 patients indicated that HCV caused the liver disease in 12 cases. Anti-HCV antibodies were more prevalent in this population of organ donors than in healthy blood donors in the US, where they are found in 0.6 percent of the samples. This may mean that these organ donors were more likely to have been involved in behavior associated with viral infections, such as intravenous drug use or promiscuity. A discussion is presented concerning the serious question of whether organs should be used from prospective donors who test positive for anti-HCV. (Consumer Summary produced by Reliance Medical Information, Inc.)

Multiple sclerosis (MS) is a progressive degenerative disease that involves the removal of the sheath of the protein myelin surrounding nerve fibers. It is an autoimmune disease, meaning that normal body components are reacted against by the immune system. The disease is thought to be due to the reactivity of T lymphocytes (white blood cells of the immune system) with myelin, as patients with MS have in their blood T cells that are reactive to myelin. Patients with MS often have particular types of histocompatibility class II antigens, DR2 and DQw1. Histocompatibility antigens are cell surface proteins that form complexes with antigens. Histocompatibility antigens are necessary for immune cells to recognize antigens, to determine if they are foreign or self and for a proper immune response to be mounted. T cells from 15,824 patients with MS, other neurological diseases, or from normal patients as controls, were grown in tissue culture. A greater number of T cells from patients with MS were reactive with a particular region of the myelin protein that formed a complex with DR2. Similar numbers of T cells from MS patients and from control subjects reacted with another region of the myelin protein that formed a complex with the histocompatibility antigen DRw11. Therefore the region that is recognized with DR2 and is reactive only in patients with MS appears to be the important region of the myelin protein that is recognized in MS. By understanding what region of the myelin protein is recognized, the course of disease can potentially be changed by altering the immune system so that this region is not recognized. This could theoretically be done by eliminating the T cells that recognize this region of the myelin protein or by inducing tolerance, so that the region would not be recognized as foreign. (Consumer Summary produced by Reliance Medical Information, Inc.)