Quantitative analysis of the acute and long-term CD4(+) T-cell response to a persistent gammaherpesvirus.
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 beta2-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 CD62Llow, with >80% maintaining that phenotype for the next 14 months. The overall conclusion is that MHV-68-specific CD4(+) T cells remain activated (CD62Llow) and at a stable frequency in the face of persistent infection.
Christensen
J P
JP
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Doherty
P C
PC
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D005260:Female; D018142:Gammaherpesvirinae / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D017735:Virus Latency / Q000276:immunology*