Single-Cell Level Response of HIV-Specific and Cytomegalovirus-Specific CD4 T Cells Correlate With Viral Control in Chronic HIV-1 Subtype A Infection

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 61; no. 1; pp. 9 - 18
• Main Authors: Eller, Michael A, Eller, Leigh Anne, Ratto-Kim, Silvia, Ouma, Benson J, Lo, Vicky, de Souza, Mark, Guwatudde, David, Nails, Barbara, Michael, Nelson L, Wabwire-Mangen, Fred, Robb, Merlin L, Marovich, Mary A, Sandberg, Johan K, Currier, Jeffrey R
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 01-09-2012; Lippincott Williams & Wilkins; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Adult; AIDS/HIV; Antigens; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Chemokine CCL4 - secretion; Chronic Disease; Cytomegalovirus - immunology; Female; Flow cytometry; Fundamental and applied biological sciences. Psychology; gag Gene Products, Human Immunodeficiency Virus - immunology; Genotype & phenotype; HIV; HIV Envelope Protein gp41 - immunology; HIV Infections - immunology; HIV Infections - virology; HIV-1 - immunology; Human immunodeficiency virus; Human viral diseases; Humans; Indexing in process; Infectious diseases; Interferon-gamma - secretion; Lymphocytes; Male; Medical sciences; Medicin och hälsovetenskap; Microbiology; Middle Aged; Miscellaneous; nef Gene Products, Human Immunodeficiency Virus - immunology; Proteins; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Virology; Viruses; Uganda; HIV-1; Immunopathology; Cytomegalovirus; CD4 T lymphocyte; memory; HIV-1 virus; Herpesviridae; Retroviridae; AIDS; T cells; Betaherpesvirinae; Immune deficiency; Lentivirus; Infection; Virus; Chronic; viral infections; Viral disease; T-Lymphocyte; Isolated cell; Human immunodeficiency virus; Subtype
• ISSN: 1525-4135; 1944-7884; 1944-7884
• DOI: 10.1097/QAI.0b013e31825c1217

BACKGROUND AND OBJECTIVE:HIV-1 subtype A is the second most prevalent subtype globally and is associated with reduced viral load, higher CD4 absolute counts, and slower disease progression. To study the possible role of T cells associated with better outcome, we examined CD4 and CD8 T-cell responses against HIV-1 and cytomegalovirus (CMV) in Ugandans infected with subtype A HIV-1.
METHODS:T-cell responses were investigated using flow cytometry and novel subtype A variant inclusive peptide (VIP) sets designed for this evaluation. CD4 T-cell responses focused primarily on Gag, whereas CD8 T-cell responses were broadly directed against Gag, gp41, and Nef VIP sets. CD4 T cells primarily responded with interferon (IFN)-γ, whereas CD8 cells were more diverse with degranulation (CD107a), IFN-γ, and macrophage inflammatory protein (MIP)-1β production.
RESULTS:No relationship was observed between CD8 T-cell responses and the HIV-1 load. Similarly, the frequency of CD4 T cells responding to these antigens did not associate with viral control. However, in CD4 T cells responding against Gag or CMV, the IFN-γ intensity, indicative of the production at the single-cell level, was inversely proportional to viral load. No significant relationship was found between T-cell effector/memory phenotype and viral control.
CONCLUSIONS:The per cell production of IFN-γ in CD4 T cells responding to HIV-1 or CMV correlated with viral control in chronic HIV-1 subtype A infection. These data suggest that quantitative aspects at the single-cell level may be more important than the frequency of antigen-specific CD4 T cells in HIV-1 subtype A infection control.