title: The expansion ability but not the quality of HIV-specific CD8(+)  T cells is associated with protective human leucocyte antigen class I alleles in long-term non-progressors.
abstract: Studies in long-term non-progressors (LTNP) have suggested that the quality of the CD8(+) response may involve protective human leucocyte antigen (HLA) class I alleles. However, studies examining the expansion ability of different functional CD8(+) T cells and their association with HLA class I alleles are lacking. LTNP, untreated typical progressors (TP) and patients successfully on highly active retroviral therapy (HAART) during 1 year (HP) were included. HLA class I typing was performed using a sequence-specific primer assay. Functional subsets of Gag- and Nef-specific CD8(+) cells were analysed based on the production of macrophage inflammatory protein (MIP)-1β, tumour necrosis factor (TNF)-α and interleukin (IL)-2. Their expansion abilities were evaluated after 10-day culture in the presence of Gag and Nef human immunodeficiency virus (HIV) peptides. No differences were seen when comparing quantitative and qualitative HIV-specific CD8(+) T cell responses according to the presence/absence of protective HLA alleles (B*58 and B*27 supertypes) in each group. However, LTNP with protective HLA alleles showed a higher expansion ability of Gag-specific MIP(+) TNF(+) IL-2(+) T cells and Nef-specific MIP(+) TNF(+) IL-2(+) . HLA-B*5701+LTNP displayed a higher expansion ability of Gag and Nef-specific MIP(+) TNF(-) IL-2(+) T cells than HLA-B*5701-LTNP. This was not so for HLA-B*2705. No differences were seen in the expansion ability according to the presence/absence of protective HLA alleles in TP and HP. The expansion ability of polyfunctional CD8(+) T cells is modulated by HLA class I alleles and targeted protein. LTNP with HLA class I protective alleles (mainly B*5701) display better expansion ability of polyfunctional HIV-specific CD8(+) T cells than the rest, suggesting that factors other than HLA-B*5701 must contribute to the control of viral replication in other LTNP. Furthermore, these attributes of HIV-specific CD8(+) T are not restored by HAART; thus, adjuvant therapies and vaccines that induce and/or normalize the expansion ability of HIV-specific T cells are required.
authors: Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain. mariolalopezvazquezdelatorre@msn.com
authors: Mariola
authors: M
authors: López
authors: Alejandra
authors: A
authors: Peris
authors: Vincent
authors: V
authors: Soriano
authors: Sara
authors: S
authors: Lozano
authors: José Luis
authors: JL
authors: Vicario
authors: Norma I
authors: NI
authors: Rallón
authors: Clara
authors: C
authors: Restrepo
authors: José M
authors: JM
authors: Benito
mesh_terms: D000328:Adult; D000483:Alleles; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D054407:Chemokine CCL4 / Q000276:immunology / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D020276:HIV Long-Term Survivors; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D015796:HLA-B27 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D054407:Chemokine CCL4; D015235:HLA-B Antigens; C464936:HLA-B*27:05 antigen; C484830:HLA-B*57:01 antigen; D015796:HLA-B27 Antigen; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus