Quantitative Analysis of the Acute and Long-Term CD4 + T-Cell Response to a Persistent Gammaherpesvirus

Abstract

The murine gammaherpesvirus 68 (MHV-68) replicates in respiratory epithelial cells, where it establishes a persistent, latent infection limited predominantly to B lymphocytes. The virus-specific CD4 + T-cell response in C57BL/6 mice challenged intranasally with MHV-68 is detected first in the mediastinal lymph nodes and then in the cervical lymph nodes and the spleen. The numbers of MHV-68-specific CD4 + T cells generated in congenic mice homozygous for disruption of the β 2 -microglobulin gene tended to be higher, indicating that the absence of the CD8 + set in this group resulted in a compensatory response. The peak frequency within the splenic CD4 + T-cell population may reach 1:50 in the acute response; it then drops to 1:400 to 1:500 within 4 months and stays at that level in the very long term. Sorting for L-selectin (CD62L) expression established that all virus-specific CD4 + T cells were initially CD62L low , with >80% maintaining that phenotype for the next 14 months. The overall conclusion is that MHV-68-specific CD4 + T cells remain activated (CD62L low ) and at a stable frequency in the face of persistent infection.