The spectrum of chronic CD8+ T-cell expansions: clinical features in 14 patients

• Published in: PloS one Vol. 9; no. 3; p. e91505
• Main Authors: Ghrenassia, Etienne, Roulin, Louise, Aline-Fardin, Aude, Marzac, Christophe, Féger, Frédéric, Gay, Julie, Pacanowski, Jérome, Hertig, Alexandre, Coppo, Paul
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.03.2014; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Antigens; Antiretroviral agents; Antiretroviral therapy; Aplasia; Biology; Biopsy; Blood; Bone marrow; CD4-CD8 Ratio; CD57 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Cell number; Central nervous system; Coinfection; Colon; Colony-stimulating factor; Cyclophosphamide; Cyclosporins; Cytomegalovirus; Cytopenia; Cytotoxicity; Disease; Female; Follow-Up Studies; Glands; Hematology; HIV; HIV Infections - complications; HIV Infections - immunology; Human health and pathology; Human immunodeficiency virus; Humans; Hypogammaglobulinemia; Immunocompromised hosts; Immunoglobulins; Immunology; Infections; Infiltration; Intravenous administration; Kidneys; Leukemia; Leukocytes (granulocytic); Leukocytosis - diagnosis; Leukocytosis - etiology; Leukocytosis - pathology; Leukopenia - etiology; Leukopenia - pathology; Life Sciences; Liver; Lymph nodes; Lymphocyte Count; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphocytosis - diagnosis; Lymphocytosis - etiology; Lymphocytosis - pathology; Lymphoma; Male; Medicine; Methotrexate; Middle Aged; Monoclonal antibodies; Mutation; Neutropenia; Organs; Patients; Red-Cell Aplasia, Pure - diagnosis; Red-Cell Aplasia, Pure - etiology; Red-Cell Aplasia, Pure - pathology; Senescence; Skin; Steroids; T cell receptors; Targeted cancer therapy; Viral infections
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0091505

Chronic CD8(+) T-cell expansions can result in parotid gland swelling and other organ infiltration in HIV-infected patients, or in persistent cytopenias. We report 14 patients with a CD8+ T-cell expansion to better characterize the clinical spectrum of this ill-defined entity. Patients (9 women/5 men) were 65 year-old (range, 25-74). Six patients had ≥ 1 symptomatic organ infiltration, and 9 had ≥ 1 cytopenia with a CD8(+) (>50% of total lymphocyte count) and/or a CD8(+)/CD57(+) (>30% of total lymphocyte count) T-cell expansion for at least 3 months. One patient had both manifestations. A STAT3 mutation, consistent with the diagnosis of large granular lymphocyte leukemia, was found in 2 patients with cytopenia. Organ infiltration involved lymph nodes, the liver, the colon, the kidneys, the skin and the central nervous system. Three patients had a HIV infection for 8 years (range, 0.5-20 years). Two non-HIV patients with hypogammaglobulinemia had been treated with a B-cell depleting monoclonal antibody (rituximab) for a lymphoma. One patient had a myelodysplastic syndrome with colon infiltration and agranulocytosis. The outcome was favorable with efficient antiretroviral therapy and steroids in HIV-infected patients and intravenous immunoglobulins in 2/3 non-HIV patients. Six patients had an agranulocytosis of favorable outcome with granulocyte-colony stimulating factor only (3 cases), cyclophosphamide, methotrexate and cyclosporine A, or no treatment (1 case each). Three patients had a pure red cell aplasia, of favorable outcome in 2 cases with methotrexate and cyclosporine A; one patient was unresponsive. Chronic CD8(+) T-cell expansions with organ infiltration in immunocompromised patients may involve other organs than parotid glands; they are non clonal and of favorable outcome after correction of the immune deficiency and/or steroids. In patients with bone marrow infiltration and unexplained cytopenia, CD8(+) T-cell expansions can be clonal or not; their identification suggests that cytopenias are immune-mediated. Our results extend the clinical spectrum of chronic CD8(+) T-cell expansions.