STABILITY OF VIRUS-SPECIFIC CD4(-CELL FREQUENCIES FROM ACUTE INFECTION INTO LONG-TERM-MEMORY() T)

Mice infected with viruses develop long-lasting high frequency memory CD8+ T cell pools, but much less is known about the CD4(+) T cell resp onse. FACS analysis revealed the modulation of several activation mark ers on CD4(+) T cells during an acute infection with lymphocytic chori omeningitis virus (LCMV), consistent with an activated cell phenotype, Examination of virus-specific cytokine production using ELISPOT assay s showed a significant increase in the number of IFN-gamma-secreting c ells 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 pro duced more IFN-gamma on a per cell basis, Using limiting dilution assa ys, we examined the CD4(+) T cell precursor (Thp) frequency in C57BL/6 mice infected with LCMV, The virus-specific Thp frequency increased f rom <1/100,000 in uninfected mice to a peak of similar to 1/600 in pur ified splenic CD4+ T cell populations by 10 days postinfection with LC MV. After the peak of the response, the Thp frequency decreased only a bout twofold per CD4(+) T cell to similar to 1/1200 and remained stabl e into long term memory, In contrast to the highly activated CD4(+) T cells recovered during the acute LCMV infection, the memory CD4(+) T c ells were maintained at a lower activation state as judged by cell siz e and ability to secrete IFN-gamma, Thus, like the CD8(+) T cell frequ encies, the CD4(+) T cell frequencies remain elevated after the acute infection subsides and stay elevated throughout long term immunity.