TH2-LIKE CD8+ T-CELLS SHOWING B-CELL HELPER FUNCTION AND REDUCED CYTOLYTIC ACTIVITY IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION

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.