Differential Requirements of Cellular and Humoral Immune Responses forFv2-Associated Resistance to Erythroleukemia and for Regulation of Retrovirus-Induced Myeloid Leukemia Development

Elimination of Friend Retrovirus in the Absence of CD8+T Cells

“…However, infectious centers were detected in the above-described reports with monoclonal antibody 720 (23) that reacts only with the helper component of FV, Friend murine leukemia virus (F-MuLV), but not with the pathogenic component, the spleen focus-forming virus (SFFV). In our recent work (24), SFFV was eliminated from B6 mice by 2 weeks after infection, and CD8 ϩ T cell-deficient B6 mice remained resistant to FV-induced disease development. Thus, the increase of F-MuLV infectious centers after CD8 ϩ T cell depletion, albeit statistically significant, may not reflect pathologically significant changes in SFFV load.…”

Class Switch Recombination and Somatic Hypermutation of Virus-Neutralizing Antibodies Are Not Essential for Control of Friend Retrovirus Infection

“…FV consists of replication-competent Friend murine leukemia virus (FMuLV) and defective spleen focus-forming virus (SFFV). In C57BL/6 (B6) mice homozygously possessing the resistant Fv2 allele (4), not only is SFFV-induced proliferation of infected erythroid progenitor cells limited, but they are also actively eliminated by cellular immune responses (5). CD4 ϩ T cells are required for SFFV elimination, while B-lymphocytes are required for F-MuLV elimination (5,6).…”

“…As virus particles in the plasma might not be detected by the above-described focus-formation assays in the presence of antiviral Ab, viral RNA was extracted from 20 l of each plasma sample using an RNeasy Plus kit (Qiagen, Valencia, CA) and eluted into 40 l of RNase-free water, and 11 l of each eluate was used for cDNA synthesis using the oligo(dT) 20 primer and a SuperScript III first-strand synthesis system (Life Technologies, Carlsbad, CA). Real-time PCR assays for the quantification of the F-MuLV genome were performed as described previously (5). At 4 weeks pi, the level of the F-MuLV genome was below the limit of detection in 4 of the 5 infected WT mice, while low levels of the F-MuLV genome were detectable in the plasma samples from infected AID Ϫ/Ϫ mice ( Fig.…”

“…In C57BL/6 (B6) mice homozygously possessing the resistant Fv2 allele (4), not only is SFFV-induced proliferation of infected erythroid progenitor cells limited, but they are also actively eliminated by cellular immune responses (5). CD4 ϩ T cells are required for SFFV elimination, while B-lymphocytes are required for F-MuLV elimination (5,6). FV-susceptible (BALB/c ϫ B6)F 1 (CB6F 1 ) mice rapidly develop splenomegaly and succumb to leukemia within 2 months postinfection (pi), but they can be protected against FV by a single immunization with an F-MuLV-encoded CD4 ϩ T cell epitope, Env 462-479 (7).…”

“…AID-deficient (AID Ϫ/Ϫ ) B6 and BALB/c mice were purchased from Riken BioResource Center, Tsukuba, Japan, and bred and maintained along with B cell-deficient MT/MT mice (5 (Fig. 1B).…”