Chronic graft-vs-host disease (GVHD) is a major cause of morbidity and mortality of long-term survivors of allogeneic hematopoietic cell transplantation (HCT). Chronic GVHD can have features of an autoimmune collagen vascular disease with clinical manifestations similar to autoimmune scleroderma and systemic lupus erythematosus (SLE). However, the pathogenesis of chronic GVHD is poorly understood. It is unclear how autoreactive T and B cells are generated in chronic GVHD recipients. We IntroductionChronic graft-versus-host disease (GVHD) is a serious and common long-term complication of allogeneic hematopoietic cell transplantation (HCT) occurring in 20% to 70% of patients surviving more than 100 days after HCT. [1][2][3][4] Despite improvements in the practice of allogeneic HCT over the last 25 years, there has been little change in the incidence, morbidity, and mortality of this complication. 3 One of the difficulties in combating chronic GVHD is the poor understanding of its pathogenesis.Chronic GVHD differs from acute GVHD in many aspects. First, the onset of acute GVHD is usually at 1 to 2 months following transplantation but the onset of chronic GVHD is usually delayed until 4 to 6 months after transplantation. 3 Second, although the target organ tissues of chronic GVHD are significantly overlapped with that of acute GVHD (ie, skin, gut, liver, and lung), the histopathology is distinguishably different. 3 While acute GVHD shows donor lymphocyte infiltration and host tissue-cell apoptosis and necrosis in target organs, chronic GVHD is featured by a marked increase in collagen deposition and a lack of T-lymphocyte infiltration in the target organ tissues. 3,4 Third, up to 70% of chronic GVHD patients have elevated levels of serum autoantibodies (eg, antinuclear, anti-dsDNA, and anti-smooth-muscle antibodies), 1,5,6 and depletion of B cells ameliorates refractory chronic GVHD in some patients. 3,7,8 Therefore, chronic GVHD has features similar to autoimmune collagen vascular disease such as scleroderma and systemic lupus erythematosus (SLE). 1,9 However, it is unclear how the autoimmune responses develop in chronic GVHD.Several murine HCT models have been used to study the pathogenesis of chronic GVHD. The first type of model is transplantation of parental lymphocytes into nonirradiated major histocompatibility complex (MHC)-mismatched F1 recipients. 10,11 In those models, the F1 recipients developed high levels of serum anti-dsDNA and glomerulonephritis, and the production of autoantibodies is a result of a cognate interaction between donor CD4 ϩ T cells and host B cells. [10][11][12][13][14][15] However, it is not clear whether the mechanisms revealed in those models reflect the pathogenesis of chronic GVHD in the irradiated HC transplant recipients.The second type of model is transplantation of donor lymphocytes into MHC-matched but minor antigen-mismatched irradiated recipients. In one model, donor LP/J (H-2 b ) bone marrow and spleen cells were transplanted into lethally irradiated C57BL/6 (H-2 b ) re...

Our findings suggest a potentially novel therapeutic approach to seasonal, zoonotic avian, and pandemic influenza-the use of phosphoantigens to activate gammadelta T cells against influenza virus infections.

As shown in humanized mice, a population of Vγ9Vδ2 T cells can reduce the severity and mortality of disease caused by infection with human and avian influenza viruses.