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

Background/aim: T lymphocytes are important players of the immune response. B-CLL is characterized by several immune defects. Our study aims to characterize the distinct maturational and functional T/NK cell subsets within B-cell chronic lymphocytic leukemia disease Rai stages. Patients and methods: Peripheral blood mononuclear cells from 43 patients enrolled in the study (16 females and 27 males, aged 68±10, 8 Rai 0, 22 Rai 1/2 and 13 Rai 3/4) were analyzed by multiparameter flow cytometry. Distinct subsets within the CD4+ (naive, central memory, effector/peripheral memory, regulatory-Tregs, follicular-TFH, CXCR3+ and/or CCR4+), CD8+ (naive+memory, effector, senescent) and NK (CD57+ and/or CD94+) were identified and compared between disease Rai stages. Results: Total numbers of T lymphocytes increase with disease stage. Both CD4+ and CD8+ T cells are elevated in absolute counts. The majority of CD4+ T cells are antigen-experienced, with increased Tregs, TFH and CXCR3+ (Th1-associated profile) T cell counts. The CD8+ T cells expansion is due mostly to the senescent CD57+ subset. No significant difference within NK subsets was observed among different disease stages. Conclusions: B-CLL behaviour seems to be associated with increased numbers of TFH and Tregs. The therapeutic modulation of T cell response in B-CLL patients may play an important role in the disease behaviour and may be a key event compensating for the immunodeficiency occurring mostly in advanced stages of the disease. Obiectiv: Limfocitele T se constituie în factori celulari importanţi ai răspunsului imun. Leucemia limfocitară cronică B se caracterizează prin defecte ale sistemului imun. Studiul nostru îşi propune caracterizarea diferitelor subseturi maturative şi funcţionale limfoide T şi NK la pacienţi aflaţi în stadii distincte de boală. Material şi metoda: au fost utilizate celule mononucleate separate în gradient de densitate de la 43 de pacienţi cu LLC-B (16 femei, 27 bărbaţi, vârsta 68±10 ani, 8 în Rai0, 22 în Rai1/2 şi 13 în Rai3/4) în vederea analizei prin citometrie in flux multiparametrică. Au fost identificate şi comparate între diferite stadii Rai, subseturile limfoide T CD4+ (naive, memorie centrală, memorie periferică/efector, reglatorii, foliculare-TFH, CXCR3 şi/sau CCR4+), CD8+ (naive+memorie, efectorii, senescente) şi NK (CD57 şi/sau CD94+). Rezultate: Limfocitele T totale circulante se găsesc în numere crescute la pacienţi în stadii avansate ale bolii. Majoritatea limfocite