Independent regulation of lymphocytic choriomeningitis virus-specific T cell memory pools: relative stability of CD4 memory under conditions of CD8 memory T cell loss.
Infection of mice with a series of heterologous viruses causes a reduction of memory CD8(+) T cells specific to viruses from earlier infections, but the fate of the virus-specific memory CD4(+) T cell pool following multiple virus infections has been unknown. We have previously reported that the virus-specific CD4(+) Th precursor (Thp) frequency remains stable into long-term immunity following lymphocytic choriomeningitis virus (LCMV) infection. In this study, we questioned whether heterologous virus infections or injection with soluble protein CD4 Ags would impact this stable LCMV-specific CD4(+) Thp memory pool. Limiting dilution analyses for IL-2-producing cells and intracellular cytokine staining for IFN-gamma revealed that the LCMV-specific CD4(+) Thp frequency remains relatively stable following multiple heterologous virus infections or protein Ag immunizations, even under conditions that dramatically reduce the LCMV-specific CD8(+) CTL precursor frequency. These data indicate that the CD4(+) and CD8(+) memory T cell pools are regulated independently and that the loss in CD8(+) T cell memory following heterologous virus infections is not a consequence of a parallel loss in the memory CD4(+) T cell population.
Varga
S M
SM
Program in Immunology and Virology, University of Massachusetts Medical Center, Worcester, MA 01655, USA.
Selin
L K
LK
Welsh
R M
RM
D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016923:Cell Death / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D006478:Hemorrhagic Fever, American / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology; D007156:Immunologic Memory; D016130:Immunophenotyping; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis; D007424:Intracellular Fluid / Q000737:chemistry / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D013194:Staining and Labeling; D013234:Stem Cells / Q000276:immunology / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology; D014615:Vaccinia / Q000276:immunology
D000941:Antigens; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin