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The Journal of Immunology, 2004, 172: 2476-2486.
Copyright © 2004 by The American Association of Immunologists

HIV-1-Specific Memory CD4+ T Cells Are Phenotypically Less Mature Than Cytomegalovirus-Specific Memory CD4+ T Cells 1

Feng Yun Yue*, Colin M. Kovacs*,{ddagger}, Rowena C. Dimayuga{ddagger}, Paul Parks{ddagger} and Mario A. Ostrowski2,*,{dagger}

* Clinical Sciences Division, and {dagger} St. Michael’s Hospital, University of Toronto, and {ddagger} Canadian Immunodeficiency Research Collaborative, Toronto, Canada

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.




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