Analysis of cytotoxic T-cell subsets in three groups of HIV-1+ patients with different response to highly active antiretroviral therapy (HAART).
Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. A10290)
Magaev S, Nikolova M, Michova A, Shahov B, Beshkov D, Yankova M, Kostov K, Taskov H Central Laboratory of Immunology, National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria
Background : Cellular immune responses play a major role in protective immunity to HIV infection. Our aim was to compare the reconstitution pattern of minor CD8 T subsets defined by CD28 and CD57 expression in HIV-1+ patients with different responses to HAART. Methods : 56 treatment-naïve HIV-1+ patients receiving HAART were followed for 24 months. Three groups were defined at endpoint: A, with good immunological and virological response (n=33, deltaCD4 AC>150, log VL< 2.5); B, with discordant immunological and virological response, (n=12, deltaCD4 AC>150, log VL>2.5), C with transient response (n=11, deltaCD4 AC<150, log VL>2.5). CD8 precursor (CD28+CD57-), intermediate (CD28-CD57-) and late effector (CD28-CD57+) subsets were analyzed by multicolor flow cytometry at baseline and every 3 months thereafter. Results : At baseline the only significant difference between the groups was a lower CD4 absolute count (AC) in group C as compared to A and B (p<0.05). As a result of HAART, in groups A and B, unlike group C, a significant recovery of CD4 AC and subset balance was observed. The CD8 precursor subset increased significantly in both groups (p<0.01) and correlated with CD4 AC, despite the high viral load in group B. Interestingly, the intermediate CD8 subset was significantly higher in group B at baseline and throughout the studied period (p<0.01) as in the group of "non-responders". A significantly higher ratio intermediate / late effectors distinguished both groups with insufficient viral suppression (B, C) from good responders (p<0.01 and p<0.05 respectively). Conclusion : In case of discordant response to HAART, the dynamics of the cytotoxic T-cell subsets defined by CD28 and CD57 coexpression was similar to a poor therapy response. We propose that the ratio CD28-CD57-/CD28-CD57+ may be instrumental for monitoring the recovery of cellular immune responses in patients with increasing CD4 AC.
Keywords: AEGIS, Antiretroviral Therapy, Highly Active, HIV-1, T-Lymphocytes, Cytotoxic, Viral Load, HIV Infections, CD4 Lymphocyte Count, Antigens, CD28, T-Lymphocyte Subsets, Antigens, CD8, Antigens, CD4, Antigens, CD57, Flow Cytometry, Humans, analysis, immunology
