Depletion of CD4 ⁺ T Cells in Major Histocompatibility Complex Class II-Deficient Mice

Abstract

The maturation of T cells in the thymus is dependent on the expression of major histocompatibility complex (MHC) molecules. By disruption of the MHC class II Ab beta gene in embryonic stem cells, mice were generated that lack cell surface expression of class II molecules. These MHC class II-deficient mice were depleted of mature CD4+ T cells and were deficient in cell-mediated immune responses. These results provide genetic evidence that class II molecules are required for the maturation and function of mature CD4+ T cells.

Dichotomous effects of complete versus partial class II major histocompatibility complex deficiency on circulating autoantibody levels in autoimmune‐prone mice

“…To assess the importance of MHCII to this phenotype, SF2 mice were generated and tested at 8-9 months of age. Consistent with the profound reduction of CD4ϩ cells in non-autoimmune-prone MHCIIdeficient mice (19,20), MHCII-deficient SF2 mice harbored markedly decreased numbers of splenic CD4ϩ cells compared with those harbored by their MHCIIintact or MHCII-intermediate littermates (P Ͻ 0.001) ( Figure 3B). This resulted in decreased numbers of splenic CD3ϩ cells in MHCII-deficient SF2 mice (P Ͻ Figures 3A, C, and D).…”

“…These results are perhaps not surprising, given that antibody responses to foreign T cell-dependent antigens are blunted in MHCII-deficient mice (19,20), so antibody responses to self antigens in MHCIIdeficient mice might also be expected to be blunted. Nevertheless, MHCII-deficient mice harbor CD1-restricted CD4ϩ T cells (21), and T cell-dependent autoantibody responses can arise via a CD1-restricted (class II MHC-independent) pathway (22)(23)(24).…”

Soluble Antigen and CD40 Triggering Are Sufficient to Induce Primary and Memory Cytotoxic T Cells

“…C57BL/6TacfBr-[KO]A␤ b mice (27) were purchased from Taconic (Germantown, NY). C57BL/6-Ly-5.2 mice were obtained from Charles River (Wilmington, MA) through the National Cancer Institute animal program.…”

CCR7 Expression in Developing Thymocytes Is Linked to the CD4 versus CD8 Lineage Decision

“…All mutant mouse strains were on the C57BL/6 background unless otherwise indicated. The following mice were obtained from Taconic Farms: P14 TCR rag2 Ϫ (29), OT1 TCR rag2 Ϫ (30), and OT2 TCR rag2 Ϫ (31); 5CC7 TCR rag2 Ϫ on the B10.A and B10 background (32); DO11.10 on the BALB/c background (33); and MHC-I-deficient (␤ 2 m Ϫ/Ϫ ) (34) and MHC-II-deficient (I-A␤ Ϫ/Ϫ ) mice (35). TCR␣-deficient mice (36), F5 TCR rag1 Ϫ (37), and AND TCR rag1 Ϫ (38) were obtained from The Jackson Laboratory.…”