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Quantifying antigen-specific CD4 T cells during a viral infection: CD4 T cell responses are larger than we think
Journal article   Peer reviewed

Quantifying antigen-specific CD4 T cells during a viral infection: CD4 T cell responses are larger than we think

Daniel S McDermott and Steven M Varga
The Journal of immunology (1950), Vol.187(11), pp.5568-5576
12/01/2011
DOI: 10.4049/jimmunol.1102104
PMCID: PMC3221938
PMID: 22043009

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Abstract

The number of virus-specific CD8 T cells increases substantially during an acute infection. Up to 90% of CD8 T cells are virus specific following lymphocytic choriomeningitis virus (LCMV) infection. In contrast, studies identifying virus-specific CD4 T cell epitopes have indicated that CD4 T cells often recognize a broader array of Ags than CD8 T cells, consequently making it difficult to accurately quantify the total magnitude of pathogen-specific CD4 T cell responses. In this study, we show that CD4 T cells become CD11a(hi)CD49d(+) after LCMV infection and retain this expression pattern into memory. During the effector phase, all the LCMV-specific IFN-γ(+) CD4 T cells display a CD11a(hi)CD49d(+) cell surface expression phenotype. In addition, only memory CD11a(hi)CD49d(+) CD4 T cells make IFN-γ after stimulation. Furthermore, upon secondary LCMV challenge, only CD11a(hi)CD49d(+) memory CD4 T cells from LCMV-immune mice undergo proliferative expansion, demonstrating that CD11a(hi)CD49d(+) CD4 T cells are truly Ag specific. Using the combination of CD11a and CD49d, we demonstrate that up to 50% of the CD4 T cells are virus specific during the peak of the LCMV response. Our results indicate that the magnitude of the virus-specific CD4 T cell response is much greater than previously recognized.
 Flow Cytometry Lymphocytic choriomeningitis virus - immunology T-Lymphocyte Subsets - immunology Antigens, CD - immunology Antigens, CD - biosynthesis Cell Separation Mice, Inbred C57BL Immunophenotyping Mice, Transgenic Adoptive Transfer CD4-Positive T-Lymphocytes - immunology Lymphocyte Activation - immunology Animals Female Mice Mice, Inbred BALB C CD4-Positive T-Lymphocytes - virology Arenaviridae Infections - immunology Immunologic Memory - immunology

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