Faculty Research 1990 - 1999

Title

B cells are not essential for peripheral T-cell tolerance.

Document Type

Article

Publication Date

1996

Keywords

B-Lymphocytes: im, Cell-Death, Clonal-Deletion, Cytochrome-c: im, Enterotoxins: im, Immune-Tolerance, Immunization, Lymph-Nodes: im, cy, Lymphocyte-Transformation, Mice, Mice-Mutant-Strains, Models-Immunological, Receptors-Antigen-T-Cell-alpha-beta: ge, im, Self-Tolerance, Spleen: im, cy, Superantigens: im, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes: im

JAX Source

Proc Natl Acad Sci U S A 1996 Jan 23;93(2):951-5

Grant

AI17134/AI/NIAID, AI18785/AI/NIAID, AI22295/AI/NIAID

Abstract

Some self-reactive T cells avoid thymic tolerance and become mature peripheral cells. Nevertheless, these cells do not usually attack their hosts because T cells can be inactivated or killed, even after they are mature, by various means. The details of these processes are not fully understood; however, a number of experiments have suggested that peripheral tolerance may be induced in mature mouse T cells by exposure to antigen on resting B cells, cells that can express antigen bound to major histocompatibility complex proteins but that lack critical costimulatory molecules such as B7-1 and B7-2. Conversely, previous experiments have indicated that mature T cells can be stimulated by exposure to antigen on cells such as dendritic cells, cells that are thought to express the essential costimulatory molecules. We tested this idea in vivo by using mice that lack B cells. Unexpectedly, T-cell tolerance and antigen-induced T-cell death occurred normally in mice free of B cells. On the other hand, antigen-specific T-cell expansion in the spleens of such mice was impaired. Finally, we have recently shown that T-cell death in mice can be prevented by exposure to antigen and an inflammatory agent such as bacterial lipopolysaccharide. This was also true in mice that lacked B cells. Overall, these data show that mature T cells can be tolerized and rescued from tolerance in the absence of B cells.