CD69+ resident memory T cells are associated with graft-versus-host disease in intestinal transplantation.

Graft-versus-host disease (GvHD) is a common, morbid complication after intestinal transplantation (ITx) with poorly understood pathophysiology. Resident memory T cells (TRM ) are a recently described CD69+ memory T cell subset localizing to peripheral tissue. We observed that T effector memory cells (TEM ) in the blood increase during GvHD and hypothesized that they derive from donor graft CD69+TRM migrating into host blood and tissue. To probe this hypothesis, graft and blood lymphocytes from 10 ITx patients with overt GvHD and 34 without were longitudinally analyzed using flow cytometry. As hypothesized, CD4+ and CD8+CD69+TRM were significantly increased in blood and grafts of GvHD patients, alongside higher cytokine and activation marker expression. The majority of CD69+TRM were donor derived as determined by multiplex immunostaining. Notably, CD8/PD-1 was significantly elevated in blood prior to transplantation in patients who later had GvHD, and percentages of HLA-DR, CD57, PD-1, and naïve T cells differed significantly between GvHD patients who died vs. those who survived. Overall, we demonstrate that (1) there were significant increases in TEM at the time of GvHD, possibly of donor derivation; (2) donor TRM in the graft are a possible source; and (3) potential biomarkers for the development and prognosis of GvHD exist.

The advantage of specific intravenous immunoglobulin (sIVIG) on regular IVIG: experience of the last decade.

During the last decade it has been shown that some components of intravenous immunoglobulin (IVIG) are responsible for their broadly therapeutic application. Currently, such specific subfractions are defined as specific IVIG (sIVIG) and are affinity-purified from commercial IVIGs that target specific antigens/antibodies related to a specific autoimmune disease. A remarkable example of the therapeutic potential of sIVIG is the proven enhanced anti-inflammatory potency of sialylated and recombinant sialylated IVIG obtained from total IVIG. In other experimental models, it has also been demonstrated that sIVIG work in many other contrivances, such as revealing anti-idiotypic networks blocking pathogenic antibodies ameliorating disease activity. sIVIG has also been shown to exert its action by modulating specific receptors expressed on immune cells in both inflammatory and autoimmune diseases. Indeed, sIVIG has emerged as a novel approach to treat different immune-mediated conditions in a more accurate antigen-specific manner. Herein we review experimental evidence supporting sIVIG-efficacy in treating autoimmune diseases and inflammation.