Th2-like CD8+ T cells showing B cell helper function and reduced cytolytic activity in human immunodeficiency virus type 1 infection.

• DOI: 10.1084/jem.180.2.489
• Publication Date: 2004-06-24T07:56:10Z
• Authors: E Maggi; M G Giudizi; R Biagiotti; F Annunziato; R Manetti; M P Piccinni; P Parronchi; S Sampognaro; L Giannarini; G Zuccati; S Romagnani
• Keywords: Cytotoxicity, Immunologic; B-Lymphocytes; CD8 Antigens; HIV Infections; T-Lymphocytes, Helper-Inducer; HIV infection; CD8+ cells; Th2 cells; B cells; Clone Cells; 3. Good health; 03 medical and health sciences; Phenotype; 0302 clinical medicine; CD4 Antigens; HIV-1; Cytokines; Humans; Interleukin-4; Job Syndrome

We analyzed at clonal level the functional profile of circulating or skin-infiltrating T lymphocytes from two individuals infected with the human immunodeficiency virus type 1 (HIV-1), suffering from a Job's-like syndrome (eczematous dermatitis, recurrent skin and sinopulmonary infections, and hypergammaglobulinemia E) and showing virtually no circulating CD4+ T cells. Most of the CD3+ T cell clones generated from both patients were CD4- CD8+ TCR alpha beta +. The others were CD4- CD8- TCR alpha beta + which exhibited reduced mRNA expression for the CD8 molecule or no mRNA expression for either CD4 or CD8 molecules. The great majority of both CD4- CD8+ and CD4- CD8- did not produce interferon (IFN) gamma and exhibited reduced cytolytic activity. Rather, most of them produced large amounts of both interleukin (IL) 4 and IL-5 and provided B cell helper function for IgE synthesis. These data suggest that a switch of cytolytic CD8+ T cells showing a Th1-like cytokine secretion profile to cells that make Th2-type cytokines, exhibit reduced cytolytic potential, and provide B cell helper function can occur in the course of HIV-1 infection. These cells may contribute to the reduced defense against viral infections and intracellular parasites and account for the elevated IgE serum levels, eosinophilia, and the allergic-like clinical manifestations seen in a proportion of HIV-1-infected individuals.