HIV-1-specific memory CD4+ T cells are phenotypically less mature than cytomegalovirus-specific memory CD4+ T cells.
HIV-1-specific CD4(+) T cells are qualitatively dysfunctional in the majority of HIV-1-infected individuals and are thus unable to effectively control viral replication. The current study extensively details the maturational phenotype of memory CD4(+) T cells directed against HIV-1 and CMV. We find that HIV-1-specific CD4(+) T cells are skewed to an early central memory phenotype, whereas CMV-specific CD4(+) T cells generally display a late effector memory phenotype. These differences hold true for both IFN-gamma- and IL-2-producing virus-specific CD4(+) T cells, are present during all disease stages, and persist even after highly active antiretroviral therapy (HAART). In addition, after HAART, HIV-1-specific CD4(+) T cells are enriched for CD27(+)CD28(-)-expressing cells, a rare phenotype, reflecting an early intermediate stage of differentiation. We found no correlation between differentiation phenotype of HIV-1-specific CD4(+) T cells and HIV-1 plasma viral load or HIV-1 disease progression. Surprisingly, HIV-1 viral load affected the maturational phenotype of CMV-specific CD4(+) T cells toward an earlier, less-differentiated state. In summary, our data indicate that the maturational state of HIV-1-specific CD4(+) T cells cannot be a sole explanation for loss of containment of HIV-1. However, HIV-1 replication can affect the phenotype of CD4(+) T cells of other specificities, which might adversely affect their ability to control those pathogens. The role for HIV-1-specific CD4(+) T cells expressing CD27(+)CD28(-) after HAART remains to be determined.
Yue
Feng Yun
FY
Clinical Sciences Division, and St Michael's Hospital, University of Toronto, Toronto, Canada.
Kovacs
Colin M
CM
Dimayuga
Rowena C
RC
Parks
Paul
P
Ostrowski
Mario A
MA
D023241:Antiretroviral Therapy, Highly Active; D018106:CD28 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002469:Cell Separation; D003587:Cytomegalovirus / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D013194:Staining and Labeling; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis
D018106:CD28 Antigens; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma