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Department of Pathology, University of Massachusetts Medical Center, Worcester, MA 01655
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-
-secreting cells in the
spleen during an acute LCMV infection. CD8+ T cells made up
the majority of the IFN--producing cells, but analysis of the cell
culture supernatants by ELISA showed that the CD4+ T cells
produced more IFN- 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
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
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-. 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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