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Benign monoclonal expansion of CD8+ lymphocytes in HIV infection
  1. Penelope R Smith1,
  2. Jamie D Cavenagh2,
  3. Tim Milne2,
  4. Denise Howe4,
  5. Susanna J Wilkes2,
  6. Paul Sinnott3,
  7. Greta E Forster1,
  8. Matthew Helbert3
  1. 1Department of Genitourinary Medicine, Royal Hospitals NHS Trust, Whitechapel, London E1 1BB, UK
  2. 2Department of Haematology, Royal Hospitals NHS Trust
  3. 3Immunopathology Clinical Group, Royal Hospitals NHS Trust
  4. 4Leukaemia Research Unit, Taunton and Somerset NHS Trust, Musgrove Park Hospital, Taunton, Somerset TA1 5DA, UK
  1. Dr Cavenagh


Background—A transient expansion of the CD8+ T cell pool normally occurs in the early phase of HIV infection. Persistent expansion of this pool is observed in two related settings: diffuse infiltrative lymphocytosis syndrome (DILS) and HIV associated CD8+ lymphocytosis syndrome.

Aim—To investigate a group of HIV infected patients with CD8+ lymphocytosis syndrome with particular emphasis on whether monoclonality was present.

Methods—A group of 18 patients with HIV-1 infection and persistent circulating CD8+ lymphocytosis was compared with 21 HIV positive controls. Serum samples were tested for antinuclear antibodies, antibodies to extractable nuclear antigens, immunoglobulin levels, paraproteins, human T lymphotropic virus type 1 (HTLV-1), Epstein-Barr virus, and cytomegalovirus serology. Lymphocyte phenotyping and HLA-DR typing was performed, and T cell receptor (TCR) gene rearrangement studies used to identify monoclonal populations of T cells. CD4+ and CD8+ subsets of peripheral blood lymphocytes were purified to determine whether CD8+ populations inhibited HIV replication in autologous CD4+ cells.

Results—A subgroup of patients with HIV-1 infection was found to have expanded populations of CD8+ T cell large granular lymphocytes persisting for 6 to 30 months. The consensus immunophenotype was CD4− CD8+ DRhigh CD11a+ CD11c+ CD16− CD28± CD56− CD57+, consistent with typical T cell large granular lymphocytes expressing cellular activation markers. Despite the finding of monoclonal TCR gene usage in five of 18 patients, there is evidence that the CD8+ expansions are reactive populations capable of mediating non-cytotoxic inhibition of HIV replication.

Conclusions—A subgroup of HIV positive patients has CD8+ lymphocytosis, but despite the frequent occurrence of monoclonal TCR gene usage there is evidence that this represents an immune response to viral infection rather than a malignant disorder.

  • HIV infection
  • CD8+ lymphocytosis
  • clonality

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