MTX withdrawal and observation for a short period should be considered in the initial management of patients who develop LPD while on MTX therapy. Responses were consistently observed, but not limited to patients in whom EBV was detected by ISHS or PCR. Further studies are required to confirm these findings and to evaluate the role for EBV in LPD that occur in patients receiving MTX.
EBV infection is more common in patients with systemic lupus erythematosus (SLE) than in control subjects, suggesting that this virus plays an etiologic role in disease and/or that patients with lupus have impaired EBV-specific immune responses. In the current report we assessed immune responsiveness to EBV in patients with SLE and healthy controls, determining virus-specific T cell responses and EBV viral loads using whole blood recall assays, HLA-A2 tetramers, and real-time quantitative PCR. Patients with SLE had an ∼40-fold increase in EBV viral loads compared with controls, a finding not explained by disease activity or immunosuppressive medications. The frequency of EBV-specific CD69+ CD4+ T cells producing IFN-γ was higher in patients with SLE than in controls. By contrast, the frequency of EBV-specific CD69+ CD8+ T cells producing IFN-γ in patients with SLE appeared lower than that in healthy controls, although this difference was not statistically significant. These findings suggest a role for CD4+ T cells in controlling, and a possible defect in CD8+ T cells in regulating, increased viral loads in lupus. These ideas were supported by correlations between viral loads and EBV-specific T cell responses in lupus patients. EBV viral loads were inversely correlated with the frequency of EBV-specific CD69+ CD4+ T cells producing IFN-γ and were positively correlated with the frequencies of CD69+ CD8+ T cells producing IFN-γ and with EBV-specific, HLA-A2 tetramer-positive CD8+ T cells. These results demonstrate that patients with SLE have defective control of latent EBV infection that probably stems from altered T cell responses against EBV.
Prophylactic antiviral therapy may reduce the sensitivity of peripheral monitoring for B lymphoproliferation, but the dramatic reduction in PTLD incidence strongly supports its use among transplant recipients at risk.
In the initial stage of cutaneous T-cell lymphoma (CTCL), proliferating CTCL cells are concentrated in the epidermis in close association with an immature dendritic cell (DC), the Langerhans cell. Because long-term in vitro culture of CTCL cells has proven difficult, the in vivo association with the major antigen-presenting cell (APC) of the epidermis has been postulated to play a role in directly stimulating the clonal T-cell proliferation. We report that CTCL cells can be reproducibly grown in culture for 3 months when cocultured with immature DCs. CTCL cells retain the phenotype and genotype of the initial malignant clone, whereas the APCs are a mixture of immature and mature DCs. CTCL cell and DC survival was dependent on direct membrane contact. Growth was inhibited by antibodies that bound to the T-cell receptor (TCR) or interfered with the interaction of CD40 with its ligand on the CTCL cell. Addition of antibody to CD3 or the clonotypic TCR caused rapid CTCL cell apoptosis followed by engulfment by avidly phagocytic immature DCs and subsequent DC maturation. The opportunity to study CTCL cells and immature DCs for prolonged periods will facilitate studies of tumor cell biology and will allow investigation of the intriguing hypothesis that CTCL cell growth is driven through TCR recognition of class II–presented self-peptides. In addition, the culture of CTCL cells will permit evaluation of therapies in vitro before clinical intervention, thereby improving safety and efficacy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.