HIV rebound after discontinuation of antiretroviral therapy increases and expands HIV-specific CD8+ responses but has no impact on its functionality.
A higher functionality of CD8(+) T cells might contribute to low-level HIV replication in long-term nonprogressors (LTNPs). However, the contrary could also be true, being the function of CD8(+) T cells modulated by HIV replication. We tested whether enhanced HIV replication following antiretroviral therapy interruption could modify the functional profile of HIV-specific CD8(+) responses. Production of MIP-1beta, IL-2, TNF-alpha, and CD107 expression by CD8(+) T cells in response to Gag and Nef optimal peptide pools was analyzed using polychromatic flow cytometry in nine HIV-infected individuals followed for 12 months after discontinuation of antiretroviral therapy. At baseline, CD8(+) T cell subsets with the greatest contribution to response were MIP-beta(+)TNF-alpha(-)IL-2(-)CD107(+) and MIP-beta(+)TNF-alpha(-)IL-2(-)CD107. Most responses were mediated by subsets expressing only one or two molecules. After 12 months of discontinuing antiretroviral therapy, no significant differences were observed in the functional profile of Gag- and Nef-specific CD8(+) responses. However, viral rebound induced a significant increase in the heterogeneity of Gag-specific CD8(+) responses. In summary, viral replication following discontinuation of antiretroviral therapy has no significant impact on qualitative aspects of HIV-specific CD8(+) responses. Thus, a higher functionality of CD8(+) responses does not seem to be the consequence of low-level virus replication.
López
Mariola
M
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
Rallón
Norma
N
Soriano
Vincent
V
Rodríguez
Isabel
I
Valencia
Eulalia
E
Labarga
Pablo
P
Moreno
Victoria
V
Vispo
Eugenia
E
Roncal
Fernando
F
González-Lahoz
Juan
J
Benito
José M
JM
D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054407:Chemokine CCL4 / Q000096:biosynthesis; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008137:Longitudinal Studies; D052118:Lysosomal-Associated Membrane Protein 1 / Q000096:biosynthesis; D052119:Lysosomal-Associated Membrane Protein 2 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019562:Viral Load; 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; D052118:Lysosomal-Associated Membrane Protein 1; D052119:Lysosomal-Associated Membrane Protein 2; D014409:Tumor Necrosis Factor-alpha; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus