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Biomedical subjects

M M Griffiths

Publications and source records attributed to M M Griffiths.

At least 55 records · Page 3Linked to original sources
PubMed1995

Polymorphism of the MHC class II Eb gene determines the protection against collagen-induced arthritis.

Collagen-induced arthritis (CIA) is an animal model of auto immune polyarthritis, sharing similarities with rheumatoid arthritis (RA). Paradoxally, susceptibility to mouse CIA is controlled by the H2A loci (DQ homologous) while RA is linked to HLA.DR genes (H2E homologous). We recently showed that the E beta d molecule prevents CIA development in susceptible H2q mice. We addressed the question of whether H2Eb polymorphism will influence CIA incidence as HLA.DRB1 polymorphism does in RA. In F1 mice, only H2Ebd and H2Ebs molecules showed protection. Using recombinant B10.RDD (Ebd/b) mice, we found that CIA protection was mediated by the first domain of the E beta d molecule. Using peptides covering the third hypervariable region of the E beta chain, we found a perfect correlation between presentation of E beta peptides by the H2Aq molecule and protection on CIA. Therefore, the mechanism by which H2Eb protects against CIA seems to rely on the affinity of E beta peptides for the H2Aq molecule.

Amino Acid Sequence↗
PubMed1995

Expression of an ovalbumin-specific V beta 8.2 TCR transgene inhibits collagen arthritis in B10.Q mice.

Previous studies have illustrated the importance of T cells bearing alpha beta TCRs in the induction and development of collagen induced arthritis (CIA) in mice. However, the scope of TCR usage in CIA has yet to be clearly defined. Given the inherent diversity of the TCR repertoire, the relative flexibility of the arthritogenic TCR repertoire specific for type II collagen (CII) is not clear. Therefore, we chose to examine the influence of a highly skewed TCR repertoire on CIA. Arthritis susceptible B10.Q (H-2q) mice were mated with C57L (H-2b) animals expressing an ovalbumin-specific V beta 8.2 TCR transgene (Tg) and Tg+ offspring were further backcrossed to B10.Q. Homozygous H-2q/q, V beta 8.2 Tg+ mice displayed a high level of V beta 8.2+ T cells in peripheral blood. However, expression of some endogenous V beta TCR, such as V beta 14, was still detected. Upon immunization with bovine CII in adjuvant, V beta 8.2 Tg+ mice were highly resistant to CIA when compared with Tg- littermates. Analysis of sera demonstrated a marked reduction in antibody specific for homologous mouse CII as well as heterologous bovine CII in Tg+ animals. Interestingly, V beta 8.2 Tg+ mice still mounted good antibody responses following immunization with human thyroglobulin, indicating that the skewed TCR repertoire affected anti-CII but not antithyroglobulin responses. Thus, our findings show that constraints placed on the TCR repertoire inhibit pathogenic responses against CII and suggest that in H-2q mice the arthritogenic TCR repertoire bears only limited flexibility.

Animals↗
PubMed1995

Identification of a cyanogen bromide fragment of porcine type II collagen capable of modulating collagen arthritis in B10.RIII (H-2r) mice.

Previous studies directed towards identifying epitopes on type II collagen (CII) important in collagen induced arthritis (CIA) in mice have focused primarily on responses mounted in susceptible H-2q strains. However, the nature of T and B cell responses against CII in susceptible H-2r strains remains ill-defined. In an effort to identify regions on CII important in CIA in H-2r mice, we examined the cellular and humoral response of susceptible B10.RIII (H-2r) mice against cyanogen bromide (CB)-cleaved fragments of porcine CII. Following immunization with native porcine CII, LNC from B10.RIII mice mounted proliferative responses predominantly to peptide CB10, while negligible proliferation was detected against fragment CB9, 7, CB8, CB11 or CB12. In contrast, sera from arthritic B10.RIII mice displayed a heterogeneous pattern of reactivity against porcine CII, with strong antibody binding measured against the major fragments CB11, CB8 and CB10. To determine the in vivo significance of the dominant cellular response to CB10, B10.RIII mice received an i.v. injection of soluble CB10 seven days before immunization with native porcine CII. Mice pretreated with CB10 were highly resistant to CIA compared to control animals. Interestingly, B10.RIII mice pretreated with fragment CB11, a region of CII implicated in H-2q restricted CIA, remained susceptible to arthritis induction. Collectively, our findings indicate that the CB10 region of porcine C11 bears determinants which may be important in the induction and/or regulation of CIA in the H-2r haplotype.

Adjuvants, Immunologic↗
PubMed1995

Altered development of collagen induced arthritis in T cell receptor V beta congenic B10.RIII mice.

Analysis of the mouse T cell receptor (TCR) V beta genome has revealed the existence of two distinct genotypes which bear deletions of certain V beta genes. Mice bearing the V beta a genotype lack approximately 50% of the V beta genome while V beta c mice lack 70% of the known V beta genes. Studies of the experimental model collagen induced arthritis (CIA) have indirectly suggested that the presence of truncated V beta genotypes may influence susceptibility to this autoimmune disease. In order to confirm the influence of V beta a and V beta c genotypes on CIA, we derived mice congenic for the known V beta haplotypes in the CIA susceptible B10.RIII (H-2r) background. Flow cytometric analysis of splenic lymphocytes revealed normal T cell levels in both B10.RIII-V beta congenic lines. Expectedly, a generalized increase in the expression of some non-deleted V beta genes was detected. In addition, the mice were immunized with porcine type II collagen and monitored for CIA. B10.RIII-V beta a mice showed little difference in arthritis incidence or severity versus B10.RIII, but a significant delay in the onset of CIA was seen. In contrast, B10.RIII-V beta c mice showed a marked decrease in arthritis incidence versus B10.RIII and the severity of CIA in arthritic mice was also significantly lower (p < 0.01). Thus, in the B10.RIII strain, the presence of truncated TCR V beta genotypes alters the development of CIA. These findings may shed light on the influence of TCR genotypes in the induction and development of human rheumatoid arthritis.

Animals↗
PubMed1995

Type XI and II collagen-induced arthritis in rats: characterization of inbred strains of rats for arthritis-susceptibility and immune-responsiveness to type XI and II collagen.

To determine the relationship between susceptibility to bovine type XI and II (BXI and BII) collagen-induced arthritis, we immunized 14 inbred and one outbred strains of rats with BXI and BII. Susceptibility to BXI-arthritis corresponded largely with susceptibility, or resistance, to BII-arthritis. LEW, BB, WF, DA, and WKY were readily susceptible to BXI- and BII-arthritis. Likewise, BII-resistant F344 and BN rats were BXI-resistant. Some strains responded differently to BXI and BII. BUF and COP, which are moderately susceptible to BII, were BXI-resistant, whereas the BII-resistant rats, DA.1N and WF.1N, were partially susceptible to BXI. (F344 x BN) F1 hybrids responded to both collagens suggesting gene complementation. Arthritis occurred in all strains producing the highest titer antisera (LEW, WF and BB). Antibody responses to BXI and BII were generally commensurate within individual strains. DA were susceptible to arthritis but produced low levels of antibody comparable to BN rats which were arthritis-resistant. BXI and BII-susceptibility was variable in rats producing intermediate antibody responses. Antibodies to RXI were detected in all BXI-immunized rats, whereas antibodies to RV and RII were uniformly weaker. DTH to RXI and RII was strong in both groups of rats, correlating poorly with arthritis and antibody responses. These studies show that phenotypic susceptibility to BXI- and BII-arthritis are largely concordant among inbred rat strains but clear differences exist in certain strains; multiple genes are likely involved.

Animals↗
PubMed1995

Collagen-induced arthritis in mice: synergistic effect of E. coli lipopolysaccharide bypasses epitope specificity in the induction of arthritis with monoclonal antibodies to type II collagen.

DBA/1 mice develop a chronic peripheral arthritis after immunization with type II collagen termed collagen-induced arthritis. We have localized the main arthritogenic determinants of CB11, a CNBr-generated arthritogenic fragment of chick type II collagen (CII), using 3 smaller peptide fragments of CB11 generated by endoproteinase LysC, LysC1 (CII 124-290), LysC2 (CII 291-374) and LysC3 (CII 375-402) and a panel of monoclonal antibodies (mAb) specific to CB11. MAb specific to the arthritogenic region of CB11 were also used to study the synergistic effect of E. coli lipopolysaccharide (LPS) on antibody-mediated arthritis in naive DBA/1 mice. LysC2 contained a minimum essential arthritogenic fragment of type II collagen: LysC2 induced arthritis by active immunization, also, a combination of four mAb specific to LysC2 passively transferred arthritis to naive mice. A single i.p. injection of LPS (50 micrograms/mouse) reduced the threshold values of the arthritogenic dose of mAb from 1 mg to 50 micrograms/clone per mouse, and decreased the number of mAb required for inducing arthritis from 4 to 2 clones. These observations suggest that LysC2, an 84 amino acid residue fragment, contains the main arthritogenic determinants within chick CB11. Importantly, LPS, a strong inducer of pro-inflammatory cytokines, negates the required multiple epitope specificity of autoantibodies in the passive transfer model and acts synergistically in the induction of arthritis by autoantibody.

Animals↗
PubMed1995

Immunologic assessment during treatment of rheumatoid arthritis with anti-CD5 immunoconjugate.

OBJECTIVE: To determine if sustained immunologic effects occurred after treatment of patients with rheumatoid arthritis (RA) with an immunoconjugate of murine anti-CD5 monoclonal antibody with ricin A chain (anti-CD5). METHODS: We measured lymphocyte populations, mitogen induced peripheral blood mononuclear cell (PBMC) stimulation, cytokine levels, immunoglobulin levels, in vivo immune function, and clinical outcomes in 9 patients with RA treated with anti-CD5. RESULTS: The treatment of patients with RA with anti-CD5 was associated with marked acute depletion of peripheral blood lymphocytes (p < 0.01) during and immediately after treatment. A sustained decrease in the number of CD3, CD4, CD5, and CD8 bearing lymphocytes persisted for 2 months after treatment (p < 0.05). After 3 months a mild decrease in the number of these lymphocyte populations persisted, but when compared to baseline values, the differences were not found to be statistically significant. Phytohemagglutinin induced PBMC proliferation was decreased at the 3-month followup (p < 0.05). Evaluations of mitogen induced cytokine and immunoglobulin production, immunoglobulin level, autoantibody, and in vivo antibody response to tetanus toxoid did not show any consistent change from baseline. CONCLUSION: Anti-CD5 treatment of RA appears to be associated with a decrease in the population of cells bearing CD5, but does not appear to induce any persistent immunologic abnormalities.

Adolescent↗
PubMed1994

Protective role of major histocompatibility complex class II Ebd transgene on collagen-induced arthritis.

Collagen-induced arthritis (CIA) is an animal model of autoimmune inflammatory polyarthritis that has features similar to rheumatoid arthritis (RA). Much like RA, susceptibility to mouse CIA is influenced by the major histocompatibility complex (MHC), H-2, and restricted to the H-2q and H-2r haplotypes. Whereas the role of the H-2A molecule in susceptibility to CIA is well established, little is known about the role of H-2E molecule in the disease. In this study, we analyzed the effect of a transgenic E beta d molecule on CIA susceptibility in a recombinant mouse B10.RQB3, which expresses the CIA susceptible Aq genes and an Eak gene, but does not produce an E molecule since Ebq is nonfunctional. In the presence of an Ebd transgene, a viable E molecule is generated. Whereas B10.RQB3 were susceptible to CIA, B10.RQB3-E beta d+ showed a dramatic reduction in the incidence of arthritis as well as a decrease in the level of anti-mouse and anti-bovine CII antibodies in their serum. No clear cut differences in the expression of T cell receptor (TCR) V beta was observed between E beta d+ and E beta d- transgenic mice. Mechanisms underlying the protective effect of E beta d transgenic molecule on CIA may shed light on how HLA-DR molecules influence human RA.

Animals↗
PubMed1994

Collagen-induced arthritis and TCRs in SWR and B10.Q mice expressing an Ek alpha transgene.

B10.Ek alpha transgenic mice were mated with H2-E B10.Q and SWR mice. F1 and F1 x parental strain backcross progeny were tested for arthritis and autoimmune reactivity to mouse type II collagen (MII) after immunization with bovine, chick, deer, or human type II collagen. The results were correlated with the H-2 haplotype (b/q vs q/q) and the TCR V beta profile of peripheral blood T cells in each mouse. Hybrid progeny expressed TCR profiles different from either parent because of the TCR V beta genomic deletions of SWR mice (V beta a), the wild-type TCR allele of C57Bl/10 (B10) mice (V beta b), and the intrathymic negative selection processes resulting from cell surface expression of Ek alpha-A q beta or Eb beta-Ek alpha, together with the integrated retroviral genes Mtv-9 originating in B10 mice and Mtv-7 (Mls-1a) from SWR mice. (B10.Ek alpha x SWR)F1 mice developed higher IgG anti-MII Ab titers, but much milder arthritis than (B10.E x B10.Q)F1 mice. Expression of Ek alpha did not change the level of IgG anti-MII Ab nor the degree of susceptibility to collagen-induced arthritis (CIA) in the H-2q/q and H-2b/q progeny of (B10.Ek alpha x B10.Q)F1 x B10.Q matings, indicating that the Mtv-9-reactive, TCR V beta 5+, and V beta 11+ T cells are not critical to CIA. Among bovine type II collagen-immunized (B10.Ek alpha x SWR)F1 x SWR backcross mice: 1) arthritis severity is associated with the presence of V beta b (p < or = 0.01) and expression of Ek alpha (p < or = 0.05), but not with the MHC haplotype (b/q vs q/q); 2) regression analysis showed a significant association (R = 0.99) between IgG anti-MII Ab titers and the level of Mtv-7-reactive V beta 6+ T cells that was detectable in the IgG1, but not the IgG2a subclass. The data prompt the speculation that Mtv-7-reactive V beta 6+ (or V beta 7+) T cells in (B10.EK alpha x SWR)F1 x SWR mice express Th2-type properties, and thus contribute to the combination of mild arthritis but high anti-MII Ab titers that characterize mice of SWR heritage.

Animals↗
PubMed1994

Collagen-induced arthritis in T cell receptor V beta congenic B10.Q mice.

B10.Q (H-2q) mice congenic for the truncated T cell receptor (TCR) V beta a and V beta c haplotypes were derived to examine the influence of TCR V beta genomic deletions in murine collagen-induced arthritis (CIA). Previous studies using gene complementation and segregation analyses suggested that in SWR (H-2q) mice, possession of the V beta a gene deletion results in CIA resistance. However, other studies have suggested alternative hypotheses. Thus, analysis of TCR V beta congenic mice allows for direct examination of V beta genotypes in CIA control. After immunization with bovine type II collagen, B10.Q-V beta a mice showed no difference in arthritis susceptibility, onset, or severity when compared with prototype B10.Q mice. In contrast, B10.Q-V beta c mice, which lack the V beta 6, 15, 17, and 19 families in addition to the V beta a deletion, were highly resistant to CIA. In vivo depletion of V beta 6+ T cells in B10.Q-V beta a mice significantly delayed arthritis onset suggesting that, among those V beta genes present in V beta a but absent in V beta c, V beta 6+ T cells contribute to arthritogenesis. Our findings show that, in B10.Q-V beta congenic mice, while the V beta a genotype does not prevent CIA, the highly truncated V beta c genotype renders B10.Q mice resistant to CIA. Thus, deletions within the V beta TCR genome can indeed influence CIA and suggests that the TCR repertoire displays only marginal flexibility in response to arthritogenic stimuli.

Animals↗
PubMed1994

B-1 cells in systemic autoimmune responses: IgM+, Fc epsilon Rdull B cells are lost during chronic graft-versus-host disease but not in murine AIDS or collagen-induced arthritis.

The potential role of B-1 cells (i.e. the CD5+ B cell and "sister" B cell subsets) in autoimmunity is controversial. CD5+ B cells have been shown to secrete antibodies of similar specificity as those found in many systemic autoimmune diseases; in addition, increases in CD5+ B cell frequency have been reported in patients suffering from rheumatoid arthritis, Sjögren's syndrome, myasthenia gravis, insulin-dependent diabetes mellitus and Hashimoto's thyroiditis. Whether these increases are due to expansion of B-1 lineage cells in the human or due to activation-induced expression of CD5 by conventional B cells is unclear. In the present study, we used three murine models of systemic autoimmunity: murine acquired immunodeficiency syndrome (MAIDS), chronic graft-versus-host disease (cGvHD), and collagen-induced arthritis (CIA) to determine whether increases in B-1 cell frequency are universally seen in models of autoimmunity which are mechanistically distinct. In contrast to the aforementioned human systemic autoimmune diseases which exhibit an increase in CD5+ B cell frequency, the percentage of CD5+ B cells declined in all three murine models of systemic autoimmune disease. Even though there was a decrease in the frequency of CD5+ B cells there was no change in the actual number of CD5+ B cells. Thus, the apparent decline in CD5+ B cell frequency was due to increases in either T cells, conventional Fc epsilon R+ B cells, or both. The only actual decline in a B cell subset was the loss of IgM+, Fc epsilon Rdull cells in both the spleen and peritoneal cavity of mice undergoing a chronic graft-versus-host reaction. Therefore, our data suggests that expansion of the B-1 subset does not occur as a general feature of murine systemic autoimmune disease. These observations, consistent with previous studies of Ig gene usage in autoreactive antibodies, support the view that expansion and differentiation of the CD5+ B cell subset is not a central event leading to autoantibody production.

Animals↗
PubMed1994

Exacerbation of collagen-induced arthritis in rats by rat cytomegalovirus is antigen-specific.

Collagen-Induced Arthritis (CIA) is an experimentally induced and genetically controlled animal model of chronic joint inflammation. In rats, there are informative strain differences in susceptibility to CIA. DA rats (RT1avl) develop severe CIA after immunization with bovine (BII), chick (CII), or homologous rat (RII) type II collagens. In contrast, the MHC-congenic DA. 1N(BN) and WF.1N(BN) rats (RT1n) are relatively resistant to CIA and develop moderate CIA in response to immunization with CII but not BII or RII. We previously found that simultaneous infection with rat cytomegalovirus (RCMV) greatly exacerbates the severity of arthritis that develops in BII-immunized DA rats. To examine the mechanism of RCMV amplification of CIA, the effect of simultaneous infection with RCMV on arthritis and autoimmunity to type II collagen was determined in WF.1N and DA.1N rats after immunization with BII, CII and RII. RCMV increased the incidence of CIA and the level of autoimmunity to type II collagen (skin-testing and IgG antibody titer) selectively in DA.1N and WF.1N rats immunized with CII, but not in littermates immunized with BII, although the transient reversal of CD4+/CD8+ mononuclear cell ratios in peripheral blood that is associated with RCMV infection occurred equally in both BII- and CII- immunized DA.1N rats. Likewise, RCMV infection moderately increased the levels of anti-RII autoimmunity and arthritis in DA rats sub-optimally immunized with RII but had no consistent effect on either anti-RII immunity or arthritis in RII-immunized DA.1N and WF.1n rats. The data show that RCMV augments arthritis only in rats that are genetically susceptible to CIA and that are appropriately immunized with a species of type II collagen that is arthritogenic for the MHC-haplotype being tested. Two possible mechanisms are suggested by these data: RCMV-associated increases in anti-RII autoimmunity in rats with CIA may result from amino acid sequence homologies between RCMV and type II collagen; alternatively, virus-induced pro-inflammatory cytokines may activate RII-reactive lymphocytes thereby potentiating autoimmunity and arthritis.

Animals↗
PubMed1993

Suppression of adjuvant-induced arthritis in DA rats by incomplete Freund's adjuvant.

OBJECTIVE: To define the effects of incomplete Freund's adjuvant (ICFA) on subsequent arthritis induced by complete Freund's adjuvant (CFA) and type II collagen (CII) in DA and Lewis rats. METHODS: ICFA was injected into DA and Lewis rats before CFA or CII injection. RESULTS: DA rats previously injected with ICFA had significantly less severe arthritis induced by CFA compared with those not receiving ICFA pretreatment (P < 0.01). ICFA had no significant impact on CFA-induced arthritis in Lewis rats or on CII-induced arthritis in DA rats. CONCLUSION: The injection of ICFA alone specifically suppresses subsequent CFA-induced arthritis in DA rats, but not in Lewis rats.

Animals↗
PubMed1993

Induction of autoimmune arthritis in rats by immunization with homologous rat type II collagen is restricted to the RT1av1 haplotype.

OBJECTIVE: To test for genetic differences in susceptibility to homologous (rat) type II collagen-induced arthritis (RII-CIA). METHODS: Nine inbred and RT1-congenic rat strains were immunized with native rat type II collagen and evaluated for arthritis and IgG anti-RII serum antibody titers. RESULTS: Only RT1av1 strains developed a high incidence of severe RII-CIA and high titers of IgG anti-RII serum antibody. Rats having RII-CIA-resistant haplotypes, RT1u,n,l (which are known to develop CIA after immunization with heterologous type II collagen), were shown to also be susceptible to passive transfer of CIA with immune serum concentrates. Clinical expression of RII-CIA was down-regulated by non-RT1 genes of BN origin. No strong gender differences in anti-RII autoimmune responses were observed. CONCLUSION: Arthritogenic, autoimmune reactivity to homologous RII is under strict genetic control but occurs readily in RT1av1 rats.

Animals↗
PubMed1993

Triggering and exacerbation of autoimmune arthritis by the Mycoplasma arthritidis superantigen MAM.

OBJECTIVE: It has been postulated that superantigens might play a role in the human rheumatic diseases, by activation of self-reactive T cells or by induction of autoantibodies. The Mycoplasma arthritidis superantigen MAM, which is derived from a naturally occurring murine arthitogenic mycoplasma, uses certain V beta chains of the murine T cell receptor (TCR) that have been proposed to be involved in murine collagen-induced arthritis (CIA). The present study was designed to determine whether MAM influences the course of arthritis mediated by immunization with porcine type II collagen (PII). METHODS: MAM or phosphate buffered saline (PBS) was injected locally or systemically into mice convalescing from CIA or mice suboptimally immunized with collagen. RESULTS: In contrast to PBS, MAM caused an exacerbation of arthritis in mice that were recovering from CIA. MAM also triggered arthritis onset in mice that had been suboptimally immunized with PII up to 160 days previously. Injection of MAM during the onset phase of CIA also triggered and enhanced the severity of arthritis in mice given low doses of PII. CONCLUSION: MAM can both trigger and exacerbate murine autoimmune arthritis induced by immunization with type II collagen. Since T cells bearing the same V beta TCRs as are used by MAM have been found to comprise a major portion of the activated cells in the synovial tissue of patients with rheumatoid arthritis, it is possible that superantigens similar to MAM may play a role in this human disease.

Animals↗
PubMed1993

Effects of gold sodium thiomalate, cyclosporin A, cyclophosphamide, and placebo on collagen-induced arthritis in rats.

The prophylactic and therapeutic effects of gold sodium thiomalate, cyclosporin A, cyclophosphamide, and placebo on collagen-induced arthritis (CIA) were evaluated in DA rats. Prophylactic treatment with cyclosporin A and cyclophosphamide suppressed the arthritis incidence, clinical inflammation, destructive bone changes, and development of anti-collagen antibody in DA rats subsequently injected with porcine type-II collagen. Therapeutic treatment with cyclosporin A and cyclophosphamide had a definite suppression on established CIA when started 21 days after the initial collagen injection, but the suppression was less marked than that of prophylactic treatment. Gold had no impact on CIA in DA rats when administered either prophylactically or therapeutically.

Animals↗
PubMed1993

T-cell receptors and collagen induced arthritis in H-2r mice.

Mouse strains B10, B10.RIII, RIIIS/J and the F1 and backcross progeny arising from them were tested for susceptibility to porcine type II collagen-induced arthritis (PII-CIA). The clinically severe arthritis of rapid onset that is characteristic of PII-immunized B10.RIII mice developed predominantly in hybrid offspring that had inherited at least one copy of wild type T cell receptor (TCR) genes (V beta b genotype) from the B10 or B10.RIII parent. The results indicate that, in the development of PII-CIA, mice expressing the H-2r/r haplotype preferentially utilize TCR V beta genes that are normally encoded within the TCR V beta genomic deletion region of RIIIS mice (V beta c). After aggressive immunization with PII, the use of alternative TCR V beta genes, encoded outside of the RIIIS deletion region, produced a high IgG antibody response that was cross-reactive with mouse type II collagen (MII) and equivalent to that of B10.RIII mice, but only a very mild, late onset arthritis of 56% (27/48) incidence in RIIIS male mice and 28% (10/35) incidence in RIIIS female mice. In comparison, B10.RIII mice routinely developed early onset of PII-CIA of significantly higher incidence (100%; p < 0.005) and four-fold greater severity, even after milder immunization protocols. The data are compatible with the proposal that the clinically weak CIA response of RIIIs mice may be primarily antibody driven while the severe CIA of B10.RIII mice reflects the added inflammatory effects of collagen-reactive effector-T cells in the joint.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗