Changes in Thymic Recent Output Function in Patients with B-Cell Lymphocytic Malignancy.

Since 1998 the use of signal joint T cell receptor excision circles (sjTRECs) to study changes in the frequency of recent thymic emigrants was reported, this study drew attention to the fact that the level of sjTRECs can be used to estimate the recent thymic output function. Therefore, sjTRECs was used as a new marker for analysis of thymic output function in different immunodeficiency diseases, immune reconstitution in patients after stem cell transplantation. Defects of cellular immunity, however, may also play a role in hematologic malignancies. Little is known about the feature of T-cell immune state in B-cell lymphocytic malignancy. In order to identify number of naïve T-cells in B-cell lymphocytic malignancy, sjTRECs-content was determined in the mononuclear cell fraction and the sjTRECs-number was related to the number of T-cells (according to the number of CD3-positive cells). Quantitative analysis of sjTRECs in DNA of peripheral blood T cells from 45 cases with B-cell lymphocytic malignancy (including 17 cases with ALL, 4 cases with CLL, 15 cases with B-NHL and 6 cases with MM) were preformed by real-time PCR and TaqMan analysis, and 14 normal individuals as controls. The results showed a dramatic reduction of sjTRECs values in patients. Some cases no sjTRECs copies could be detected in 40000 T cells. The mean value of sjTRECs was 0.39±0.75 copies/1000 PBMCs in ALL, 0.11±0.15 copies/1000 PBMCs in B-CLL, 0.67±1.39 copies/1000 PBMCs in B-NHL, 0.91±1.16 copies/1000 PBMCs in MM patients, as compared with 4.1±3.65 copies/1000 PBMCs in normal individuals, the sjTRECs level in all goups of B-cells lymphocytic malignancy were significant decrease (p=0.0001, p=0.048, p=0.002) except MM group (p=0.053). However, when comparison of the sjTRECs value in CD3+ compartments, it was not statistically different from the sjTRECs counts between patients with ALL (3.91±7.20 copies/1000 CD3+cells) and normal individuals (6.36±5.28 copies/1000 CD3+cells) (p=0.2139), suggesting that the reduction of sjTRECs level in patients wit ALL may due to lower numbers of T cells in peripheral blood. In conclusions, the results suggest that some thymic dysfunction in T cell generation was detected at least in most patient with B-cell lymphocytic malignancy. However, whether this is due to clonal expansion of T-cells to antigens, or reflects impairment of immune function associated to the malignancy, remains an open question. In a prospective study sjTRECs levels will be determined in different T- cell compartments including CD45RA+, CD4+ and CD8+ cells and so on.