Abstract
BackgroundT-cell immunodeficiency is a common feature in cancer patients, which may relate to initiation and development of tumor. Based on our previous finding, to further characterize the immune status, T cell proliferative history was analyzed in CD4+ and CD8+ T cells from chronic myeloid leukemia (CML) patients.MethodsQuantitative analysis of δRec-ψJα signal joint T cell receptor excision circles (sjTRECs) was performed in PBMCs, CD3+, CD4+ and CD8+T cells by real-time PCR, and the analysis of 23 TRBV-D1 sjTRECs was performed by semi-nested PCR. Forty eight CML cases in chronic phase (CML-CP) were selected for this study and 17 healthy individuals served as controls.ResultsThe levels of δRec-ψJα sjTRECs in PBMCs, CD3+, CD4+, and CD8+ T cells were significantly decreased in CML patients, compared with control groups. Moreover, the numbers of detectable TRBV subfamily sjTRECs, as well as the frequency of particular TRBV-BD1 sjTRECs in patients with CML were significantly lower than those from healthy individuals.ConclusionsWe observed decreased levels of recent thymic emigrants in CD4+ and CD8+ T cells that may underlay the persistent immunodeficiency in CML patients.
Highlights
T-cell immunodeficiency is a common feature in cancer patients, which may relate to initiation and development of tumor
Decreased level of δRec-ψJα signal joint T cell recombination excision circles (sjTRECs) in peripheral blood mononuclear cells (PBMCs), CD4+ and CD8+ cells from chronic myeloid leukemia (CML) patients The absolute numbers of sjTRECs and RAG2 were measured in two independent assays and sjTREC content per 1000 PBMCs was calculated using a formula n = 2 × 1000 × [sjTREC(1)+sjTREC(2)]/[RAG2(1)+RAG2(2)] [15]
In comparison with the sjTRECs in healthy individuals (3.76 ± 3.42 copies/1000 PBMCs, 5.87 ± 4.96 copies/1000 CD3+ cells, 5.62 ± 6.45 copies/1000 CD4+ T cells, 6.79 ± 7.1 copies/ 1000 CD8+T cells), a dramatic reduction of sjTRECs values was found in patients with CML
Summary
T-cell immunodeficiency is a common feature in cancer patients, which may relate to initiation and development of tumor. Based on our previous finding, to further characterize the immune status, T cell proliferative history was analyzed in CD4+ and CD8+ T cells from chronic myeloid leukemia (CML) patients. T cell differentiation in the thymus is characterized by a hierarchical order of rearrangement steps in the TCR genes, resulting in the joining of one of multiple variable (V), diversity (D), and joining (J) gene segments. This results in each differentiating T cell expressing unique TCR on the surface. In addition to the formation of the V(D)J coding joint, each of the TCR rearrangement steps generates circular episomal DNA fragments - signal joint T cell recombination excision circles (sjTRECs). Rearrangement between two TRD deleting elements, δRec and ψJα, produces a δRec-ψJα signal joint TRECs [5,6,7,8,9]. sjTRECs are assumed to have a high over-
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