title: 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.
abstract: 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.
authors.affiliation: Instituto Nacional de Parasitología Dr. Mario Fatala Chabén, Buenos Aires, Argentina.
authors.forename: R J
authors.initials: RJ
authors.lastname: Argüello
authors.forename: J
authors.initials: J
authors.lastname: Balbaryski
authors.forename: G
authors.initials: G
authors.lastname: Barboni
authors.forename: M
authors.initials: M
authors.lastname: Candi
authors.forename: E
authors.initials: E
authors.lastname: Gaddi
authors.forename: S
authors.initials: S
authors.lastname: Laucella
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D019562:Viral Load
chemical_list: D001323:Autoantibodies; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit