Lymphopenia-induced proliferation of CD4 T-cells is associated with CD4 T-lymphocyte exhaustion in treated HIV-infected patients

• Published in: Indian journal of medical research (New Delhi, India : 1994) Vol. 147; no. 4; pp. 376 - 383
• Main Authors: Saidakova, Evgeniya, Shmagel, Konstantin, Korolevskaya, Larisa, Shmage, Nadezhda, Chereshnev, Valeriy
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.04.2018; Medknow Publications and Media Pvt. Ltd; Scientific Scholar; Medknow Publications & Media Pvt Ltd
• Subjects: Acquired immune deficiency syndrome; AIDS; Antigens; Antiretroviral drugs; Care and treatment; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cell division; Cell Proliferation; HIV; HIV infection; HIV Infections - drug therapy; HIV Infections - immunology; Human immunodeficiency virus; Humans; Immunology; Immunophenotyping; Infections; Infectious diseases; Leukocytes, Mononuclear; Lymphocyte Activation; Lymphocytes; Lymphocytopenia; Lymphopenia; Original; Physiological aspects; Senescence; T cells; T-Lymphocyte Subsets; Viral Load; United States > US; Russia; CD57 - exhaustion - HIV infection - lymphopenia - PD-1 - proliferation - T cell
• ISSN: 0971-5916
• DOI: 10.4103/ijmr.IJMR_1801_15

Background & objectives: Under the lymphopenic condition, T-cells divide to maintain their peripheral pool size. Profound chronic lymphopenia in some treated HIV-infected patients, characterized by poor T-cell recovery, might result in intensive homeostatic proliferation and can cause T-cell exhaustion and/or senescence. The present study was undertaken to evaluate the homeostatic proliferation of CD4+T-cells in treated HIV-infected individuals, and to determine the amount of phenotypically exhausted and senescent CD4 T-lymphocytes. Methods: Thirty seven treated HIV-infected patients with suppressed HIV viral load (<50 copies/ml) were studied. Patients were divided into two groups: immunological non-responders (INRs) with CD4+T-cells <350/μl (n=16) and immunological responders (IRs) with CD4+T-cells >350/μl (n=21). T-cell subsets [naïve, central memory (CM), and effector memory (EM)] and proportions of cycling (Ki-67+), senescent (CD57+) and exhausted (PD-1+) T-lymphocytes were assessed using flow cytometry. Results: CD4+T-cell cycling rate was higher in INRs than in IRs due to more extensive proliferation of CM, 4.7 vs 2.7 per cent (P <0.01) and EM, 4.8 vs 3.2 per cent (P <0.05). The percentages of CD4+Ki-67+ CM and EM T-lymphocytes were inversely related to the CD4+T-cell counts in the appropriate subset, r=-0.584 (P <0.001) and r=-0.556, (P <0.001), respectively. Exhaustion [24.2 vs 16.7% (P <0.01)], but not senescence [7.1 vs 10.8% (P>0.05)] was more pronounced in the INR group than in the IR group. The frequency of CD4+Ki-67+ CM T-cells was related to the proportion of CD4+PD-1+ cells of the same subset, r=0.789 (P <0.001). The numbers of CD4+Ki-67+PD-1+ CM and EM T-cells were substantially higher in INRs than in IRs. Interpretation & conclusions: The present data indicated that intensive homeostatic proliferation contributed to the T-cell exhaustion in HIV-infection.