The antigen-specific CD8+ T cell repertoire in unimmunized mice includes memory phenotype cells bearing markers of homeostatic expansion

Memory T cells exhibit superior responses to pathogens and tumors compared with their naive counterparts. Memory is typically generated via an immune response to a foreign antigen, but functional memory T cells can also be produced from naive cells by homeostatic mechanisms. Using a recently developed method, we studied CD8 T cells, which are specific for model (ovalbumin) and viral (HSV, vaccinia) antigens, in unimmunized mice and found a subpopulation bearing markers of memory cells. Based on their phenotypic markers and by their presence in germ-free mice, these preexisting memory-like CD44hi CD8 T cells are likely to arise via physiological homeostatic proliferation rather than a response to environmental microbes. These antigen-inexperienced memory phenotype CD8 T cells display several functions that distinguish them from their CD44lo counterparts, including a rapid initiation of proliferation after T cell stimulation and rapid IFN-γ production after exposure to proinflammatory cytokines. Collectively, these data indicate that the unprimed antigen-specific CD8 T cell repertoire contains antigen-inexperienced cells that display phenotypic and functional traits of memory cells

Increased B cell deletion and significantly reduced auto-antibody titre due to premature expression of human complement receptor 2 (CR2, CD21)

The involvement of complement receptor 2 (CR2) in B cell tolerance and autoimmune disease has been revealed over the past decade or so. Our previous studies have established that mice prematurely expressing human CR2 under the control of a lambda light chain promoter (in particular the hCR2high line) have a marked deficit in their immune response to various antigens and fail to develop collagen-induced arthritis. This phenotype appears to be the result of irreversible changes in B cell signalling pathways and suggested that hCR2 expressing mice are protected from developing autoimmune disease. To test this hypothesis, we examined the ability of the hCR2 to block the development of spontaneous autoimmune disease on the C57BL/6j-Faslpr/Faslpr (B6lpr) background. We found that expression of hCR2 on the B6lpr background resulted in a significant reduction in levels of anti-nuclear antibodies (ANA) generated as mice aged but the levels of ANA were still higher than those found in age matched C57BL/6j (B6) mice. B cells from hCR2high mice were found to display a higher baseline level of apoptosis, whether analysed ex vivo or after in vitro culture, than their B6 counterparts and this was apparently linked to both surface IgM expression by the B cells and C3 levels in the mice. Our data also provides evidence that B cell survival in the presence of hCR2 is heavily modified by the background strain of the mouse. Overall, we have demonstrated that mice expressing hCR2 on their B cells during bone marrow development display a higher degree of apoptosis which may lead to a deletion of autoreactive B cells and be protective against the development of autoimmune disease