Restricted heterogeneity in T-cell antigen receptor V beta gene usage in the lymph nodes and arthritic joints of mice.

Abstract

We have used PCR to study the expression of T-cell antigen receptor 13 RNA containing particular variable region (V) elements from transcripts directly in the cells isolated from joints and lymph nodes of B1O.Q mice (H-2r) immunized with chicken type II collagen. Our data show that the T cells present in arthritic joints expressed only a few '$ transcripts -'2, -6, -7, -8.2, -9, -10, and -15. 6 and -8.2 were expressed predominantly (six out ofseven animals) while others were expressed at a relatively low level in different animals. In lymph node cells, transcripts for $j6, -8.2, and -9 were detected in four out of seven animals. The data indicate that in collageninduced arthritis there is a restrictive usage of TCR $ elements and that *6 and -8.2 are probably used preferentially.Collagen-induced arthritis (CIA) was first described by Trentham et al. (1) in 1977 and has subsequently been induced in mice and primates (2, 3). CIA ensues after immunization of susceptible strains of mice and rats with type II collagen in Freund's adjuvant (1, 2). The arthritic lesions in this model bear resemblance to some of the lesions of rheumatoid arthritis in man. Both the cellular and T-cell-dependent immune responses to type II collagen are critical for the pathogenesis of the disease (4).Susceptibility to the development of an autoimmune disorder has been found to have a distinct genetic basis, both in humans and in animal models of the disease. In mouse, induction of CIA is linked to the major histocompatibility complex (MHC) and has been mapped to the I-A subregion by using various recombinant strains, and it has been shown that only H-2 and H-2r haplotypes develop CIA after immunization with type II collagen (4, 5). In other haplotypes, immunization with heterologous type II collagen induces an autoantibody response but never progresses to the development of arthritis (6, 7). These results indicate that the induction of CIA is dependent on the activation of I-A-restricted self-type-II-collagen-reactive T cells. Furthermore, in another study, Seki et al. (8) have proposed that there is a synergistic effect between humoral and cell-mediated immunity on the induction and perpetuation of CIA.We have earlier reported that the T-cell antigen receptor (TCR) variable region 18 chain (Vs) genes apparently play a vital role in the susceptibility to the induction of CIA (9). We have also shown that inbred strains of mice with the susceptible MHC haplotype but with the genomic deletion of TCR Vp genes were resistant to the induction of arthritis, indicating that TCR Vp genes play an important, perhaps crucial, role in the pathogenesis of arthritis (10-12). In this communication, we report that the T cells present in arthriticjoint and draining lymph nodes (LNs) of mice express a restricted repertoire of TCR Vp genes.MATERIALS AND METHODS Mice. B10.Q mice (H-2q) were bred and maintained in the mouse colony at Mayo Clinic (Rochester, MN). Male mice (6 to 8 weeks old) were used in the present study. Age-and sex-matched mic...

Triggering and exacerbation of autoimmune arthritis by the mycoplasma arthritidis superantigen mam

“…The present study showed that VpS-negative (RIIIS x C57BR)F, mice also develop arthritis (Table I), and other studies indicate that RIIIS mice which lack both Vp6 and Vp8 develop a mild, transient CIA (30). Recent work by Haqqi et al supports these findings and suggests that Vp6, Vp8.2, Vp7, and Vp9 are involved in CIA since these T cells are the ones most commonly found in the joints and draining lymph nodes of Bl0.Q mice with CIA (33).…”

“…In the CIA model, mice or rats immunized with heterologous or homologous collagen develop an acute-to-chronic polyarthritis thought to be mediated by T cells that are cross-reactive with self collagen as well as by an antibody response to specific collagen epitopes (23)(24)(25)(26)(27). T cells bearing the Vp8 TCRs have been shown to play a major role in CIA (18,28), and there is some evidence that other TCRs, such as Vp5, Vp6, and Vp7, may also be involved, especially in mouse strains that lack VpS (28)(29)(30)(31)(32)(33).…”

Potentiation of lymphomagenesis by methylnitrosourea in mice transgenic for LMO1 is blocked by O6-alkylguanine DNA-alkyltransferase

“…All lymphomas had evidence of a T-cell lineage by one of these markers. Likewise, clonality was determined by TCRb rearrangement and expression as described (Haqqi, et al 1992). All lymphomas had TCRb clonal rearrangments by Southern analysis (data not shown).…”

Analysis of T cell receptor Vβ usage in the autoimmune sialadenitis of non-obese diabetic (NOD) mice

“…The hypofunction of the salivary and lachrymal glands in autoimmune disease is due to lymphocytic infiltration, in which it is generally assumed that autoreactive T cells recognize unknown self-antigen and play a central role in the pathogenesis of SS [22]. Clonally expanded T cell populations having restricted usage of TCR gene segments may be essential to the pathogenesis of autoimmune diseases [23,24]. The restriction of TCR repertoire may play an important role in T cell recognition of unknown self antigen through a possible restrictive usage of TCR Vb genes in various autoimmune diseases, both in humans and rodents.…”