Altered frequency and phenotype of CD4 + forkhead box protein 3 + T cells and its association with autoantibody production in human immunodeficiency virus-infected paediatric patients

The association between immune dysfunction and the development of autoimmune pathology in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is not clear. The frequency and phenotype of regulatory T cells, as well as the presence of autoantibodies, were evaluated in a paediatric cohort of HIV-infected patients without clinical evidence of autoimmune disease. Lower absolute counts but higher percentages of total CD4^{+} forkhead box protein 3 (FoxP3)^{+} T cells were recorded in children with severe immunosuppression than in those without evidence of immunosuppression. The frequencies of classical CD4^{+}CD25^{+}FoxP3^{+} regulatory T cells were not altered, whereas CD4^{+}FoxP3^{+}CD25^{-} T cells were found increased significantly in patients with severe immunosuppression. Like classical regulatory T cells, CD4^{+}FoxP3^{+}CD25^{-} T cells display higher cytotoxic T-lymphocyte antigen 4 (CTLA-4) but lower CD127 expression compared with CD4^{+}FoxP3^{–}CD25^{+} T cells. An improvement in CD4^{+} T cell counts, along with a decrease in viral load, was associated with a decrease in CD4^{+}FoxP3^{+}CD25^{-} T cells. The majority of the patients with severe immunosuppression were positive for at least one out of seven autoantibodies tested and displayed hypergammaglobulinaemia. Conversely, HIV-infected children without evidence of immunosuppression had lower levels of autoantibodies and total immunoglobulins. A decline in CD4^{+}FoxP3^{+} T cell numbers or a variation in their phenotype may induce a raise in antigen exposure with polyclonal B cell activation, probably contributing to the generation of autoantibodies in the absence of clinical autoimmune disease.