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Dysregulation of CD28 and CTLA‐4 expression by CD4 T cells from previously immunodeficient HIV‐infected patients with sustained virological responses to highly active antiretroviral therapy
Author(s) -
Stone SF,
Price P,
French MA
Publication year - 2005
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2005.00307.x
Subject(s) - perforin , medicine , immunology , cd8 , cytotoxic t cell , cd28 , immune system , t cell , viral load , lentivirus , virology , human immunodeficiency virus (hiv) , biology , viral disease , biochemistry , in vitro
Objectives Current guidelines recommend commencing highly active antiretroviral therapy (HAART) in HIV‐infected patients when CD4 T‐cell counts reach 350 cells/μL. However, late‐presenting HIV‐infected patients with CD4 T‐cell counts<50 cells/μL are still common. The ability of long‐term HAART to normalize immune dysregulation in severely immunodeficient HIV‐infected patients remains unclear. Here we address indices of immune dysregulation in previously severely immunocompromised HIV‐infected patients treated with long‐term HAART who had achieved increased CD4 T‐cell counts and complete suppression of HIV viraemia. Methods We examined expression of CD28, cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) and intracellular perforin by CD4 and CD8 lymphocytes from 25 highly selected HIV‐infected patients [nadir CD4 T‐cell counts <50 cells/μL, >4 years on HAART and >6 months of complete viral suppression (<50 HIV‐1 RNA copies/mL)] and 18 HIV‐seronegative age‐ and sex‐matched controls. Results HIV‐infected patients had lower percentages of CD28‐expressing CD4 lymphocytes and higher percentages of CTLA‐4‐expressing CD4 lymphocytes than controls. The percentage of CTLA‐4‐expressing CD4 lymphocytes correlated inversely with that of CD28‐expressing CD4 lymphocytes. The proportion of CD4 lymphocytes expressing perforin was generally low. However, more HIV‐infected patients than controls had >1% of CD4 lymphocytes expressing perforin [11 of 25 (44%) vs. one of 18 (5.5%)]. The percentage of CD8 lymphocytes expressing perforin did not differ between HIV‐infected patients and controls. Amongst HIV‐infected patients, the percentage of perforin‐expressing CD8 lymphocytes correlated inversely with nadir but not current CD4 T‐cell count. Conclusions Expression of CD28, CTLA‐4 and perforin by CD4 lymphocytes remain dysregulated in HIV‐infected patients with previous severe immunodeficiency, despite increased CD4 T‐cell counts and control of HIV viraemia by HAART.