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 and Matthew Helbert³

¹ Department of Genitourinary Medicine, Royal Hospitals NHS Trust, Whitechapel, London E1 1BB, UK
² Department of Haematology, Royal Hospitals NHS Trust
³ Immunopathology Clinical Group, Royal Hospitals NHS Trust
⁴ Leukaemia Research Unit, Taunton and Somerset NHS Trust, Musgrove Park Hospital, Taunton, Somerset TA1 5DA, UK

Correspondence to:
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+ DR^high 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.

Key Words: HIV infection • CD8+ lymphocytosis • clonality

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