The Spectrum of Chronic CD8+ T-Cell Expansions: Clinical Features in 14 Patients

Abstract

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.

The diffuse infiltrative lymphocytosis syndrome (DILS). A comprehensive review

“…Furthermore, there appears to be a correlation between Gag specific CD8 þ cells and their capacity in blocking viral replication [41]. Similarly, one can hypothesize that DILS is a consequence of a non-clonal hyperfunctional CD8 þ T-cell expansion, and particularly that of a majority of CD8 þ T-cells expressing CD57 þ , as pointed out by Ghrenassia et al [20]. DILS may potentially be one among many other syndromes within the spectrum of chronic CD8 þ T-cell expansions.…”

“…Presentation is that of an acute or subacute polyneuropathy, somewhat painful and mostly involving the distal lower extremities [19]. Lumbosacral radiculoplexus neuropathy and cervico-thoracic myelitis associated with CD8 þ lymphocytic meningitis have also been reported [18,20].…”

“…Hepatitis appears to be related to periportal lymphocytic infiltration and may be associated with liver failure with portal hypertension and ascites [2,4,5,10,20]. Hepatomegaly was observed in 23% of cases [2,4].…”

“…diarrhoea) are frequent in the HIV-infected, especially in those under HAART. We recently described one patient with DILS associated with CD8 þ rectal infiltration, which was revealed by diarrhoea and tenesmus [20].…”

“…Diagnosis of DILS should be considered only in the presence of chronic HIV infection, evidence of organ-infiltration and a blood CD4 þ /CD8 þ ratio less than 1. Other autoimmune diseases need to be excluded, especially in the frequent context of Table 4 Comparing DILS to primary Sj€ ogren's syndrome and IgG4-related disease [3,5,10,20,50]. …”