Abstract
One of the key downregulators of T cell activation is CD152 (CTLA-4). Mice genetically deficient in CD152 (cd152-/- mice) develop massive expansion of both CD4+ and CD8+ T cells as well as increased numbers of splenic Ig-secreting cells and serum Ig levels. To determine the dependence of the lymphoproliferation and B cell hyperactivity on MHC class II (MHCII), MHCII-deficient (mhcii-/-) cd152-/- mice were generated. Compared to that in their mhcii+/+ counterparts, expansion of CD4+ cells in mhcii-/-cd152-/- mice was markedly attenuated. Nonetheless, expansion of CD8+ cells was identical in both sets of mice, demonstrating that the effects of CD152 deficiency on CD4+ cells can quantitatively be dissociated from those on CD8+ cells, and pointing to a critical downregulatory role for CD152 in MHCII-independent CD8+ cell activation in vivo. B cell hyperactivity also developed in mhcii-/-cd152-/- mice, albeit in a manner less rapid and less intense than that in their mhcii+/+ counterparts, demonstrating an underlying MHCII-Independent diathesis to B cell dysregulation and pointing to a critical downregulatory role for CD152 in MHCII-independent B cell activation in vivo. When human DQ8 was introduced as a transgene into mhcii-/-cd152-/- mice, B cell hyperactivity was restored to levels observed in mhcii+/+cd152-/- mice, pointing to a critical downregulatory role for CD152 in MHCII-dependent B cell activation in vivo superimposed upon its downregulatory role on MHCII-independent B cell activation.
Original language | English (US) |
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Pages (from-to) | 895-904 |
Number of pages | 10 |
Journal | International Immunology |
Volume | 16 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2004 |
Keywords
- CD4 cells
- CD8 cells
- Ig-secreting cells
- IgG
- IgM
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology