Identification of T-cell receptor V ? deletion mutant mouse strain AU/ssJ (H-2 q ) which is resistant to collagen-induced arthritis

Abstract

Our laboratory is involved in investigating the role of T-cell receptor (Tcr) in collagen-induced arthritis (CIA). During these studies we found AU/ssJ (H-2q) mice to be resistant to CIA like SWR (H-2q), as compared with other H-2q strains with wild-type Tcr like DBA/1 and B10.Q. Upon screening with monoclonal antibodies F23.1 and KJ23a, AU/ssJ was found to be F23.1 negative (V beta 8 Tcr negative) and KJ23a positive (V beta 17a Tcr positive). Southern blot analysis on liver DNA using specific Tcr-V beta probes confirmed the deletion of V beta 8 gene family and also showed that AU/ssJ mice have deletions of V beta 9, V beta 13, V beta 12, and V beta 11 genes of Tcr. Further, these mice show a restriction fragment length polymorphism pattern with V beta 10, V beta 6, and V beta 17 probes similar to SWR mice as compared with B10 mice. Since SWR and AU/ssJ are from different backgrounds, these studies indicate that specific variable region beta chain genes of Tcr are crucial for susceptibility to CIA in mice. Furthermore, these studies identify an additional inbred strain which has also deleted 50% of its Tcr-V beta genes.

Nitric oxide production during adjuvant‐induced and collagen‐induced arthritis

“…Although these 2 models have many clinical similarities, fundamental differences in their pathophysiology and genetic control are clearly evident and provide an ideal opportunity for defining and comparing the genes that control 2 different mechanisms of arthritis susceptibility. AIA is a particularly informative model because it predominantly involves T cell-mediated mechanisms (1-8), whereas CIA requires both humoral (14)(15)(16)(17)(18)(19)(20) and cellular immunity (21). CIA is characterized by the development of a symmetric erosive polyarthritis in association with the production of anticollagen antibodies (13)(14)(15)(16)(17)(18).…”

“…T cells have a dual role by promoting B cells to synthesize autoantibodies and by releasing proinflammatory cytokines. These T cell-dependent functions are controlled by antigen-specific T lymphocytes with a limited T cell receptor V, repertoire (21). This complex interaction of immunologic and inflammatory pathways in the CIA model is under polygenic control.…”

“…collagen (CII) (13)(14)(15)(16)(17)(18)(19)(20)(21), respectively. Although these 2 models have many clinical similarities, fundamental differences in their pathophysiology and genetic control are clearly evident.…”

“…Although these 2 models have many clinical similarities, fundamental differences in their pathophysiology and genetic control are clearly evident. AIA is a particularly informative model because it predominantly involves T cell-mediated mechanisms (1)(2)(3)(4)(5)(6)(7)(8), in contrast to CIA, which requires both humoral (14)(15)(16)(17)(18)(19)(20) and cellular immunity (21).…”

Genomically imposed and somatically modified human thymocyte V beta gene repertoires.

“…Thus, humans appear to differ from mice in that extensive genomic deletions have been identified encompassing approximately one-half of the total mouse Vp3 genes in at least five different inbred strains (35)(36)(37) and in wild mice from different geographic locations (38)(39)(40).…”