Papers Benign monoclonal expansion of CD8+ lymphocytes in HIV infection

Background—A transient expansion of the CD8+ T cell pool normally occurs in the early phase of HIV infection. Persist-ent expansion of this pool is observed in two related settings: diVuse infiltrative lymphocytosis syndrome (DILS) and HIV associated CD8+ lymphocytosis syn-drome. Aim—To investigate a group of HIV infected patients with CD8+ lymphocyto-sis 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 anti-gens, immunoglobulin levels, parapro-teins, human T lymphotropic virus type 1 (HTLV-1), Epstein-Barr virus, and cyto-megalovirus serology. Lymphocyte pheno-typing and HLA-DR typing was performed, and T cell receptor (TCR) gene rearrangement studies used to iden-tify monoclonal populations of T cells. CD4+ and CD8+ subsets of peripheral blood lymphocytes were purified to deter-mine whether CD8+ populations inhibited HIV replication in autologous CD4+ cells. Results—A subgroup of patients with HIV-1 infection was found to have ex-panded populations of CD8+ T cell large granular lymphocytes persisting for 6 to 30 months. The consensus immunopheno-type was CD4 − CD8+ DRhigh CD11a+ CD11c+ CD16 − CD28 ± CD56 − CD57+, consistent with typical T cell large granu-lar lymphocytes expressing cellular acti-vation markers. Despite the finding of monoclonal TCR gene usage in five of 18 patients, there is evidence that the CD8+ expansions are reactive populations capa-ble of mediating non-cytotoxic inhibition of HIV replication. Conclusions—A subgroup of HIV positive patients has CD8+ lymphocytosis, but despite the frequent occurrence of mono-clonal TCR gene usage there is evidence that this represents an immune response to viral infection rather than a malignant disorder