Lines of T Lymphocytes Induce or Vaccinate Against Autoimmune Arthritis

Objective. To analyze HLA–DR4 alleles in New Zealand Polynesians with rheumatoid arthritis (RA).Methods. Thirty Polynesians and 30 Caucasians with RA, as well as 65 Polynesian and 60 Caucasian healthy blood donors, were DR4 subtyped using the polymerase chain reaction and sequence‐specific oligonucleotide probes.Results.The frequency of DR4 (DRB1*04) was increased in both Polynesian (P <0.001) and Caucasian (P <0.005) RA patients compared with race‐matched controls. Dw4 (DRB1*0401) was detected in 15 of 30 Caucasian patients but only 2 of 30 Polynesian patients (P <0.001). In Polynesians, RA was associated with Dw15 (DRB1*0405), which was present in 11 of 30 patients and 3 of 65 controls (P < 0.001). Dw13 (DRB1*0403) was the most frequent DR4 allele in healthy Polynesians, but was not significantly associated with RA.Conclusion. The predominance of the Dw13 subtype in Polynesians may explain in part the low prevalence of RA in this population. The association of Dw15 with RA in Polynesians supports the hypothesis that the third hypervariable region of DRβ determines susceptibility to RA.

Section: Discussionmentioning

confidence: 76%

HLA–DR4 subtypes in new zealand polynesians. predominance of dw13 in the healthy population and association of dw15 with rheumatoid arthritis

Tan

Farmiloe

Roberts

et al. 1993

“…Line A2 was previously shown to be arthritogenic in heavily irradiated rats but not in control rats, provided that the line cells were activated prior to intravenous inoculation of cells (1). The arthritogenicity of anti-Mycobacterium tuberculosis (MT) line A2 was attributed to its clones, such as A2b, that recognized an antigen in cartilage proteoglycan which was cross-reactive with MT ( 2 4 ) .…”

mentioning

confidence: 99%

Histopathology of arthritis induced in rats by active immunization to mycobacterial antigens or by systemic transfer of t lymphocyte lines. a light and electron microscopic study of the articular surface using cationized ferritin

Stănescu

Lider

Eden

et al. 1987

Self Cite

We analyzed the histopathologic findings of arthritis in 3 rat models: adjuvant arthritis induced by active immunization to Mycobacterium tuberculosis (MT)i antigens, arthritis produced by passive transfer of an intrinsically arthritogenic line of anti-MT T lymphocytes, and bystander arthritis produced by intraarticular injection of a foreign antigen, ovalbumin, into rats with T lymphocyte line cells specific for the ovalbumin antigen. The histopathology of the tibiotarsal and knee joints was studied by light microscopy and the articular surface of the cartilage by electron microscopy after labeling with cationized ferritin. The lesions in the 3 models of arthritis were compared. In active adjuvant arthritis, inflammatory lesions and cartilage destruction were found as early as 9 days after immunization, and persisted for as long as 11 months. Similar, but somewhat milder, lesions were found in arthritis produced by transfer of anti-MT T lymphocytes. Inflammatory signs were present at 4 days, when there was no evidence of joint edema. Severe inflammatory lesions were found in arthritis induced by transfer of anti-ovalbumin T lymphocytes that was followed by ovalbumin injection into the knee. Pathologic changes were found to be similar in all 3 models. Thus, the changes could be attributed to the action of T lymphocytes, irrespective of whether the target antigen was intrinsic to the joint.The studies described here were undertaken to document the pathologic changes in the joints of rats in the course of active adjuvant arthritis or arthritis produced by passive transfer of lines of antigenspecific T lymphocytes. Line A2 was previously shown to be arthritogenic in heavily irradiated rats but not in control rats, provided that the line cells were activated prior to intravenous inoculation of cells (1). The arthritogenicity of anti-Mycobacterium tuberculosis (MT) line A2 was attributed to its clones, such as A2b, that recognized an antigen in cartilage proteoglycan which was cross-reactive with MT ( 2 4 ) . Bystander arthritis was induced in nonirradiated rats ( 5 ) by intravenous inoculation with activated antiovalbumin line cells. Ten days later, ovalbumin was injected directly into a knee joint. The ensuing arthritis was caused by the local reaction of the T lymphocytes to the ovalbumin in the joint. The pathologic findings were studied in these models and in active adjuvant arthritis by light and electron microscopic methods.

“…The responses were assessed by 3H-thymidine uptake. In healthy individuals (Figure l), 3H-thymidine uptake was significantly increased over background counts only when PBL from DR4+ and DR1+ individuals were stimulated with the M1 peptide (amino acid residues [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. This was detected in 5 of 7 such individuals (data from 3 subjects are shown).…”

Section: Resultsmentioning

confidence: 99%

“…Such 12 (December 1992) alter host responses to microbial agents which exhibit "molecular mimicry" to host MHC. Second, the DR4 allele of the MHC may influence the selection of the T cell repertoire during thymic development of T cells, and the T cells thus selected may include arthritogenic clones (6). Third, the DR4 molecules may be involved more directly in the pathogenesis of RA, considering that residues 70-74 are sited within the antigenrbinding groove (3 …”

mentioning

confidence: 99%

Lymphocyte responses to DR4/1‐restricted peptides in rheumatoid arthritis. The immunodominant T cell epitope on the 19‐kd mycobacterium tuberculosis protein

Tan

Farmiloe

Young

et al. 1992

Objective. Peptides presented by DR4/1 may be involved in the pathogenesis of rheumatoid arthritis (RA). T cell responses to DR4/1‐restricted peptides unrelated to the causative antigen may be altered in RA. Thus, DR4/1‐restricted lymphocyte responses in healthy volunteers and patients with RA were determined. Methods. Peripheral blood lymphocytes (PBL) and synovial lymphocytes were cultured with synthetic peptides spanning the 19‐kd Mycobacterium tuberculosis (MT) protein. Results. 3H‐thymidine uptake by PBL from 5 of 7 healthy individuals and 5 of 7 RA patients increased in response to the N‐terminal peptide (residues 1–20). Eleven fresh synovial fluid and 4 fresh synovial tissue (ST) lymphocyte samples did not proliferate in response to any of the peptides. However, the same T cell epitope was identified by ST lymphocytes when these were precultured. The N‐terminal peptide was not a common antibody‐binding site, unlike several of the other peptides. Conclusion. Similar responses by RA and normal PBL to a DR4/1‐restricted immunodominant T cell epitope on the 19‐kd MT protein were observed. The responses were more readily detected in PBL than in synovial lymphocytes. These observations may be relevant for assessing unrelated synthetic peptides in the development of DR4/1‐restricted peptide immunotherapy.