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

作者：Lopez Mariola^*; Peris Alejandra; Soriano Vincent; Lozano Sara; Luis Vicario Jose; Rallon Norma I; Restrepo Clara; Benito Jose M

来源：Immunology, 2011, 134(3): 305-313.

DOI：10.1111/j.1365-2567.2011.03490.x

• CD8(+) T cell response
• cytokines
• expansion ability
• HIV
• HLA class I
• LTNP

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)-1 beta, tumour necrosis factor (TNF)-alpha 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(star)58 and B(star)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-star 5701+LTNP displayed a higher expansion ability of Gag and Nef-specific MIP+ TNF- IL-2(+) T cells than HLA-B-star 5701-LTNP. This was not so for HLA-B(star)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(star)5701) display better expansion ability of polyfunctional HIV-specific CD8(+) T cells than the rest, suggesting that factors other than HLA-B(star)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.

• 出版日期2011-11