Chronic lymphocytic leukaemia cells drive the global CD4+ T cell repertoire towards a regulatory phenotype and leads to the accumulation of CD4+ forkhead box P3+ T cells

Abstract

Summary Advanced chronic lymphocytic leukaemia (CLL) is associated with profound immunodeficiency, including changes in T regulatory cells (Tregs

The Skewed Balance Between Tregs and Th17 in Chronic Lymphocytic Leukemia

“…Moreover, Jack et al showed that the increased frequency of Tregs in CLL patients is due to increased formation through CD27-CD70 interaction and increased resistance to apoptosis via increased levels of Bcl-2 antiapoptotic protein [71]. Following these findings, the increased frequency and absolute number of Tregs in CLL patients and its association with disease progression were demonstrated, repeatedly [72][73][74][75][76] (as shown in Table 2). …”

“…Increased frequency of both CD4+ and CD8 + Tregs which correlated with disease progression Intact function of Tregs [77] Increased frequency of CD4 + Tregs that correlated with disease progression The higher frequencies of Tregs were correlated with decreased T-cell responses against viral and tumor antigens [24] Increased frequency of CD4 + Tregs that correlated with disease progression Decreased frequency of Tregs after therapy with thalidomide [70] Increased formation of Tregs via CD27-CD70 interaction Increased resistance to apoptosis via increased levels of Bcl-2 antiapoptotic protein [71] Increased frequency of CD4 + Tregs that correlated with disease progression Tregs predict the time to initial treatment in early-stage CLL Intact function of Tregs [72] Increased frequency of CD4 + Tregs that correlated with disease progression [73,76] Increased frequency of CD4+ Tregs that correlated with disease progression Leukemic B cells induce FoxP3+ Tregs [74] The emergence of CD8 + PD-1 + replicative senescent phenotype in early stage CLL which correlated with disease progression [78] Tregs express cytotoxic markers such as CD107a and granzyme A and kill autologous leukemic B cells [79] Tregs inhibit effector T cells in part through the release of soluble CD25…”

Chronic lymphocytic leukaemia cells become both activated and immunosuppressive following interaction with CD3 and CD28 stimulated PBMC

“…The T-cells of CLL patients have been shown to exhibit features of T-cell exhaustion and have altered expression of a number of genes resulting in defective immunological synapse formation [1,[3][4][5][6][7][8]. There is however evidence from both the pattern of patient virus reactivation and in vitro studies that not all T-cell subsets in CLL patients have defective function [2,28,29].…”

“…T-cells are central to the development of anti-tumour responses and the T-cells from CLL patients have been reported to exhibit a number of defects [1,[3][4][5][6][7][8].…”

Rai stage-related changes within T/NK cell populations from B-CLL patients

“…Previous studies also described the expansion of this specific T cell compartment, a direct correlation with the disease stage, and an inverse correlation with non-regulatory T cell -mediated responses to viral or tumor antigens antigens (11,12,24).…”