Prevention of graft-versus-host disease and bone marrow rejection: kinetics of induction of tolerance by UVB modulation of accessory cells and T cells in the bone marrow inoculum

UVB irradiation (700 J/m2) of bone marrow cells (UVB-BMC) before transplantation into lethally gamma-irradiated (10.5 Gy) allogeneic rats prevents graft-versus-host disease (GVHD) and induces a stable complete lymphohematopoietic chimerism. To better understand the underlying mechanism of the development of stable chimerism and induction of tolerance to donor organs in this model, we examined if the addition of T cells or dendritic cells (DC), as antigen presenting cells (APC), would restore the immunogenicity of UVB-BMC in in vitro mixed lymphocyte reaction (MLR) and induce in vivo bone marrow (BM) graft rejection. Whereas gamma-irradiated, unfractionated BMC induce allogeneic T cells to proliferate, UVB irradiation of BMC abolishes the stimulatory capacity of such cells in a primary MLR. Addition of purified T cells, CD4+ T cells, CD8+ T cells or B cells, respectively, failed to restore the capacity of UVB-BMC to stimulate allogeneic T- cell proliferation. In contrast, the addition of only a small number of splenic accessory cells or purified DC, which by themselves were relatively ineffective in stimulating T-cell proliferation, restored the accessory function and the allostimulatory capacity of UVB-BMC. To define the molecular defect induced by UVB irradiation, cytokines were added as costimulatory factors to primary MLRs and the results showed that the addition of interleukin (IL)-2 or IL-6 but not IL-1 or interferon gamma (IFN-gamma) restored the stimulatory capacity of UVB BMC. This finding suggests that UVB may alter the production, and/or utilization of IL-2 and IL-6 either at the membrane or cytoplasmic level. Parallel in vivo studies showed that addition of DC to UVB BM inoculum resulted in failure of BM engraftment, whereas addition of T cells led to development of fatal GVHD, thus suggesting that UVB modulation of accessory cells reduces graft immunogenicity and prevents BMT rejection, while modulation of T cells prevents GVHD. Our data provide evidence that UVB modulation of APC and mature T cells contained within BMC is potentially useful in preventing GVHD without endangering successful engraftment and may serve as a model for induction of adult chimerism and tolerance without the development of GVHD.     

The unmasking of <Emphasis Type="Italic">Pneumocystis jiroveci</Emphasis> pneumonia during reversal of immunosuppression: case reports and literature review

Background  

Pneumocystis jiroveci pneumonia (PCP) is an important opportunistic infection among immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV). The clinical presentation of PCP in immunosuppressed patients have been well-reported in the literature. However, the clinical importance of PCP manifesting in the setting of an immunorestitution disease (IRD), defined as an acute symptomatic or paradoxical deterioration of a (presumably) preexisting infection, which is temporally related to the recovery of the immune system and is due to immunopathological damage associated with the reversal of immunosuppressive processes, has received relatively little attention until recently.     

Immunologic heterogeneity of diffuse large cell lymphoma

The cellular lineage of 57 diffuse large-cell lymphomas (DLCLs) was determined using a panel of monoclonal antibodies directed against lineage-restricted and -associated T, B, and monocyte antigens. The majority (82%) were of B cell lineage as determined by the expression of sig and/or B1, with the remaining 16% being of T cell lineage and 2%, of monocyte-myeloid lineage. By the expression of other B cell- restricted and -associated antigens, two major and two minor subgroups could be identified. These subgroups expressed the following phenotypes: (1) B1+B4+sIG+B2- (51%); (2) B1+B4+sIg+B2+ (29%); (3) B1+B4+sIg-B2+ (10%); and (4) B1+B4-sIg+B2- (10)%. The morphology of transformed lymphocytes, the weak to absent expression of the early B cell antigens B2 and sIgD, and the absence of the late B cell differentiation antigens PCA-1 and PC-1 suggested that these tumors were the neoplastic counterparts of normal B cells at the mid-stages of differentiation. Further support for the notion that B-DLCLs correspond to transformed B lymphocytes was concluded from the observation that B cells could be identified in normal spleen that expressed the cell surface phenotype and morphological appearance of the majority of B- DLCLs.