Benign monoclonal expansion of CD8+ lymphocytes in HIV infection
- Penelope R Smith1,
- Jamie D Cavenagh2,
- Tim Milne2,
- Denise Howe4,
- Susanna J Wilkes2,
- Paul Sinnott3,
- Greta E Forster1,
- Matthew Helbert3
- 1Department of Genitourinary Medicine, Royal Hospitals NHS Trust, Whitechapel, London E1 1BB, UK
- 2Department of Haematology, Royal Hospitals NHS Trust
- 3Immunopathology Clinical Group, Royal Hospitals NHS Trust
- 4Leukaemia Research Unit, Taunton and Somerset NHS Trust, Musgrove Park Hospital, Taunton, Somerset TA1 5DA, UK
- Dr Cavenagh
- Accepted 31 August 1999
Abstract
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.
