Impaired T-cell proliferation among HAART-treated adults with suboptimal CD4 recovery in an African cohort

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• 作者：Damalie Nakanjako (1) (2)
  Isaac Ssewanyana (3)
  Rose Nabatanzi (3)
  Agnes Kiragga (2)
  Moses R Kamya (1)
  Huyen Cao (4)
  Harriet Mayanja-Kizza (1)
  
• 关键词：T ; cell proliferation ; Immune activation ; Suboptimal immune recovery ; HAART immune responses ; HIV/AIDS
• 刊名：BMC Immunology
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：14
• 期：1
• 全文大小：537KB
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• 作者单位：Damalie Nakanjako (1) (2)
  Isaac Ssewanyana (3)
  Rose Nabatanzi (3)
  Agnes Kiragga (2)
  Moses R Kamya (1)
  Huyen Cao (4)
  Harriet Mayanja-Kizza (1)
  
  1. Makerere University College of Health Sciences, P.O. Box 7072, Kampala, Uganda
  2. Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda
  3. Joint Clinical Research Center, Kampala, Uganda
  4. California Department of Public Health, Richmond, CA, USA
  
• ISSN：1471-2172

文摘

Background Most HIV-infected subjects exhibit a progressive rise in CD4 T-cell counts after initiation of highly active antiretroviral therapy (HAART). However, a subset of individuals exhibit very poor CD4 T-cell recovery despite effective control of HIV-RNA viraemia. We evaluated CD4 T-cell proliferation among suboptimal responders and its correlation with CD4 T-cell activation. Methods The magnitude of CD4 increase (difference between absolute CD4 counts at baseline and absolute CD4 counts at 4 years of ART) was grouped into 4 quartiles for the 211 patients with sustained HIV-RNA viral suppression. Cases of ‘Suboptimal immune responders-/strong> included patients within the lowest quartile [Median CD4 increase 165 (Range ?3-298) cells/μl; n=52] and a comparison group of ‘Optimal immune responders-/strong> was defined as patients within the highest quartile of CD4 increase [Median CD4 increase 528 (Range 417-78) cells/μl; n=52]. Frozen PBMC were thawed and analysed from a convenient sample of 39 suboptimal responders and 48 optimal responders after 4 years of suppressive antiretroviral therapy. T-cell activation was measured by proportions of T-cells expressing surface marker CD38 and HLADR (CD4+CD38+HLA-DR+ and CD8+CD38+HLA-DR+ cells). T-cell proliferation was determined by the extent of carboxyfluorescein diacetate succinimidyl ester (CFSE) dye dilution on culture day 5 of PBMCs in the presence of antigen (SEB, PPD, CMVpp65, GagA and GagD). Samples were analyzed on a FACS Calibur flow cytometer and flow data was analyzed using FlowJo and GraphPad. Results Overall, CD4 T-cell proliferation on stimulation with SEB, PPD, CMVpp65, Gag A and Gag D.antigens, was lower among suboptimal than optimal responders; this was significant for SEB (CD4+ p=0.003; CD8+ p=0.048) and PPD antigens (CD8+ p=0.038). Among suboptimal responders, T-cell proliferation decreased with increasing immune activation (Negative correlation; slope = ?.13±?.11) but not among optimal responders. Conclusion T-cell immune activation and exhaustion were associated with poor proliferation among suboptimal responders to HAART despite sustained viral suppression. We recommend studies to further understand the mechanisms leading to impaired T-cell function among suboptimal responders as well as the potential role of immune modulation in optimizing CD4 count and functional recovery after HAART.