No major differences in the functional profile of HIV Gag and Nef-specific CD8+ responses between long-term nonprogressors and typical progressors.
The mechanism explaining the failure of HIV-specific CD8(+) T cell responses to successfully control HIV replication remains elusive. A total of 83 drug-naive HIV-infected individuals, 27 of whom were long-term nonprogressors (LTNP), was examined. The ability of CD8(+) T lymphocytes to produce three different cytokines (MIP-1beta, TNF-alpha, IL-2) in response to HIV Gag and Nef peptides and to polyclonal stimuli and the ability of HIV-specific CD8(+) T cells to expand in vitro were evaluated by multiparameter flow cytometry. In response to polyclonal stimulation, LTNP presented significantly higher levels of several CD8(+) T cell subsets than progressors. While most patients presented detectable Gag and Nef-specific CD8(+) responses, no significant differences in any of the CD8(+) functional T cell subsets were recognized when comparing LTNP and progressors. HIV responses were dominated by cells producing only MIP-1beta or TNF-alpha, being similar in LTNP and progressors. However, expansion of HIV-specific CD8(+) T cells was more frequent in LTNP than progressors, especially for cells producing MIP-1beta. LTNP show higher levels of CD8(+) responses against polyclonal stimuli than progressors. However, HIV-specific CD8(+) responses do not differ between them except for a more preserved ability of cells from LTNP to expand in vitro.
López
Mariola
M
Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
Soriano
Vincent
V
Lozano
Sara
S
Ballesteros
Celia
C
Cascajero
Almudena
A
Rodés
Berta
B
De La Vega
Elvira
E
González-Lahoz
Juan
J
Benito
José M
JM
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D054407:Chemokine CCL4 / Q000096:biosynthesis; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D020276:HIV Long-Term Survivors; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
C066507:CCL4 protein, human; D054407:Chemokine CCL4; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus