Constitutive expression of Fas ligand in large granular lymphocyte leukaemia

Perzova, Raisa; Loughran, Thomas P.

doi:10.1046/j.1365-2141.1997.d01-2113.x

Cited by 73 publications

(48 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The detection of increased IFN-γ expression in most of the patients with or without CTL expansions may imply that CTL-mediated pathophysiology is operative in most of the studied patients and perhaps constitutes a better marker of T-cell-mediated inhibition of hematopoiesis. In general, our results are in agreement with previous reports dealing with increased Fas-L and IFN-γ production in both CIN and LGL patients [26][27][28].…”

Section: Discussionsupporting

confidence: 93%

Clonal predominance of CD8+ T cells in patients with unexplained neutropenia

Wlodarski

Nearman

Jiang

et al. 2008

Experimental Hematology

View full text Add to dashboard Cite

Objective-T-cell-mediated autoimmunity may be involved in some cases of idiopathic neutropenia. We hypothesized that a precise T-cell receptor repertoire analysis may uncover cytotoxic T-cell (CTL) expansions that are less pronounced than those seen in T large granular lymphocyte leukemia (T-LGL), but are pathophysiologically analogous and thus can serve as markers of a T-cell-mediated process. Materials and Methods-Using rational algorithms for T-cell receptor analysis and in vivotracking of CTL responses previously established in our laboratory, we studied patients with unexplained chronic neutropenia (n = 20), T-LGL (n = 15), and healthy controls (n = 12). We further investigated the involvement of soluble inhibitory factors by coculture assays. To determine the level of immune activation, we studied interferon-g expression in CD8 + cells using Taqman polymerase chain reaction.Results-Fifteen expanded (immunodominant) CTL clones were detected in 12 of 20 patients. In comparison to LGL leukemia, these clones were less immunodominant, but clearly discernible from subclinical lymphoproliferations in controls. As a surrogate of cytotoxic activity, we found markedly increased production of interferon-γ in most of the neutropenia patients, irrespective of the presence of immunodominant CTL clones.Conclusions-These results suggest that, while immunodominant CTL clones are detectable in a proportion of patients only, CTL-mediated pathophysiology may be a general mechanism operating in idiopathic neutropenia. Oligogoclonal CTL expansions in chronic neutropenia may indicate an ongoing autoimmune process, while highly polarized monoclonalities in a subset of neutropenic LGL patients may represent the "extreme" end of the clonal continuum.Drugs, hereditary factors, infections, and intrinsic bone marrow diseases explain the etiology of most neutropenias. The inability to detect an immune-mediated process or other obvious cause often leads to diagnosis of chronic idiopathic neutropenia (CIN) [1][2][3][4][5][6]. Similarly, secondary autoimmune neutropenia (AIN), usually associated with collagen vascular diseases, lymphoproliferative disorders and viruses, is typically diagnosed by exclusion and thus relies on the quality of clinical and laboratory workups [6][7][8][9]. Lineage-restricted cytopenias, including neutropenia, have been associated with T-cell large granular lymphocyte leukemia It is likely that patients with AIN/CIN may belong to a heterogeneous group of diseases combining various autoimmune etiologies. Appearance of the bone marrow may reveal some clues as to the cellular targets of the autoimmune process; left shift could indicate that more mature cells are targets, while pure white cell aplasia suggests that very early myeloid precursors are affected. The similar target spectrum in AIN/CIN and T-LGL suggests that cytotoxic T-cell (CTL)-mediated autoimmunity can also operate in AIN/CIN. Consequently, detection of highly polarized CTL expansions in some cases of neutropenia patients may be consistent wi...

show abstract

Section: Discussionsupporting

confidence: 93%

Clonal predominance of CD8+ T cells in patients with unexplained neutropenia

Wlodarski

Nearman

Jiang

et al. 2008

Experimental Hematology

View full text Add to dashboard Cite

show abstract

“…35 FasL expression is also increased in malignant lymphomas, Hodgkin's disease and large granular lymphocyte leukemia. 46,47 Whether the increased expression of FasL contributes to the survival and growth of leukemic or dysplastic clones is unknown.…”

Section: Discussionmentioning

confidence: 99%

Fas ligand expression in the bone marrow in myelodysplastic syndromes correlates with FAB subtype and anemia, and predicts survival

et al. 1999

View full text Add to dashboard Cite

“…Various soluble effectors including Fas-ligand have also been implicated in the pathophysiology of the cytopenias in T-LGL. [20][21][22] The clonal CTL in T-LGL generally resemble an antigen-activated CD8 + CD57 + effector cell, as both constitutively express perforin and Fas-ligand and can suppress neutrophils in vitro. 21,23,24 Gene expression studies have shown that the T-LGL clone exhibits upregulation of cytotoxic proteases and adhesion molecules and downregulation of protease inhibitors.…”

Section: Introductionmentioning

confidence: 99%