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  • Title: Stability of virus-specific CD4+ T cell frequencies from acute infection into long term memory.
    Author: Varga SM, Welsh RM.
    Journal: J Immunol; 1998 Jul 01; 161(1):367-74. PubMed ID: 9647245.
    Abstract:
    Mice infected with viruses develop long-lasting high frequency memory CD8+ T cell pools, but much less is known about the CD4+ T cell response. FACS analysis revealed the modulation of several activation markers on CD4+ T cells during an acute infection with lymphocytic choriomeningitis virus (LCMV), consistent with an activated cell phenotype. Examination of virus-specific cytokine production using ELISPOT assays showed a significant increase in the number of IFN-gamma-secreting cells in the spleen during an acute LCMV infection. CD8+ T cells made up the majority of the IFN-gamma-producing cells, but analysis of the cell culture supernatants by ELISA showed that the CD4+ T cells produced more IFN-gamma on a per cell basis. Using limiting dilution assays, we examined the CD4+ T cell precursor (Thp) frequency in C57BL/6 mice infected with LCMV. The virus-specific Thp frequency increased from <1/100,000 in uninfected mice to a peak of approximately 1/600 in purified splenic CD4+ T cell populations by 10 days postinfection with LCMV. After the peak of the response, the Thp frequency decreased only about twofold per CD4+ T cell to approximately 1/1200 and remained stable into long term memory. In contrast to the highly activated CD4+ T cells recovered during the acute LCMV infection, the memory CD4+ T cells were maintained at a lower activation state as judged by cell size and ability to secrete IFN-gamma. Thus, like the CD8+ T cell frequencies, the CD4+ T cell frequencies remain elevated after the acute infection subsides and stay elevated throughout long term immunity.
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