Stability of virus-specific CD4+ T cell frequencies from acute infection into long term memory.
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.
Varga
S M
SM
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655, USA.
Welsh
R M
RM
D000208:Acute Disease; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D016207:Cytokines / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013234:Stem Cells / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines