Impaired generation of high-affinity interleukin-2 receptors in the autologous mixed lymphocyte reaction in rheumatoid arthritis

Akasu, Fumito; Poplonski, L; Snow, K. M.; Volpé, Robert; Keystone, Edward

doi:10.1016/0090-1229(92)90006-a

Cited by 3 publications

(2 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar findings are observed in other human autoimmune diseases (28,29) including human type I diabetes (30). Studies using several autoimmune rodent models also demonstrated reduced proliferation in syngeneic mixed lymphocyte reaction (SMLR) (3 1, 32).…”

Section: Discussionsupporting

confidence: 65%

Effect of 5- Dihydrotestosterone on T-cell Proliferation of the Female Nonobese Diabetic Mouse

Toyoda

Takei

Formby

1996

Experimental Biology and Medicine

View full text Add to dashboard Cite

Nonobese diabetic (NOD) mice develop type I diabetes spontaneously and have been utilized as a model for human autoimmune insulin-dependent diabetes. The disease is caused by the destruction of insulin-producing beta cells in the pancreatic islet of Langerhans by infiltrating inflammatory cells, which are primarily T lymphocytes. The incidence of diabetes in NOD mice is increased in females compared with males, suggesting that sex steroid hormones play an important role in the development of the disease. We therefore investigated the effect of a male steroid, 5-alpha-dihydrotestosterone (5DHT), on disease development, T-cell phenotype, T-cell proliferation, and cytokine profiles in this model. None of the mice that received 5DHT for 120 days (n = 7) developed insulitis, whereas all control mice (n = 8) developed the disease. The percentage of CD4+ T cells in peripheral blood mononuclear cells was markedly decreased in the 5DHT-treated females compared with those in controls (37.1 +/- 4.8 vs 51.3 +/- 9.3, P < 0.02), whereas no significant differences in the percentage of CD8+ T cells were observed between treated and control female mice. Results of a syngeneic mixed lymphocyte reaction (SMLR) also suggested that T cells are major target cells of 5DHT administration. An increased expression of IL-4 mRNA, representing T helper 2 (Th2) T cells, was observed in the SMLR. On the basis of these results, a systemic administration of 5DHT appears to have direct effects on the expansion of Th2 cell populations with subsequent restoration of normal immune responses.

show abstract

Section: Discussionsupporting

confidence: 65%

Effect of 5- Dihydrotestosterone on T-cell Proliferation of the Female Nonobese Diabetic Mouse

Toyoda

Takei

Formby

1996

Experimental Biology and Medicine

View full text Add to dashboard Cite

show abstract

“…The proliferative response of T cells toward irradiated autologous APCs in the AMLR is dependent on the expression of MHC class II and costimulatory molecules (12), requires irradiation of APCs for the induction of T cell proliferation (13,14), and is thought to represent autoreactivity to autoantigens. However, despite the presumably autoreactive T cell repertoire in RA, RA patients have been found to show a profoundly impaired proliferative response as well as impaired generation of high-affinity IL-2Rs in the AMLR (15)(16)(17)(18).…”

Section: R Heumatoid Arthritis (Ra)mentioning

confidence: 99%

Ex Vivo Homeostatic Proliferation of CD4+ T Cells in Rheumatoid Arthritis Is Dysregulated and Driven by Membrane-Anchored TNFα

Wagner

Pierer

Wahle

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

The systemic CD4+ T cell compartment in patients with rheumatoid arthritis (RA) is characterized by TCR repertoire contraction, shortened telomere lengths, and decreased numbers of recent thymic emigrants, suggesting a disturbed CD4+ T cell homeostasis. In mice, homeostatic proliferation of peripheral CD4+ T cells is regulated by TCR interaction with self peptide-MHC complexes (pMHC) and can be reproduced in vitro. We have established an ex vivo model of homeostatic proliferation, in which self-replication of human CD4+ T cells is induced by cell-cell contact with autologous monocytes. In healthy individuals, blockade of TCR-pMHC class II contact resulted in decreased CD4+ T cell division. In contrast, homeostatic proliferation in RA patients was not inhibited by pMHC blockade, but increased during the initial culture period. The anti-TNF-α Ab cA2 inhibited homeostasis-driven ex vivo proliferation in healthy controls and in RA patients. In addition, treatment of RA patients with infliximab decreased the ex vivo rate of homeostatic proliferation of CD4+ T cells. Our results suggest a disturbed regulation of CD4+ T cell homeostasis leading to the repertoire aberrations reported in RA. Membrane-anchored TNF-α appears to be a cell-cell contact-dependent stimulus of homeostatic proliferation of CD4+ T cells, possibly favoring self-replication of autoreactive CD4+ T cells in patients with RA.

show abstract

Lymphocyte Function in Early‐Onset Periodontitis

Engel¹

1996

Journal of Periodontology

View full text Add to dashboard Cite

This is a limited review of recent research on the role of lymphocytes in earlyonset periodontitis (EOP). EOP lesions are histologically characterized by a dense infiltrate of lymphocytes. The role of lymphocytes in these lesions is unclear, but recent evidence suggests that there may be alterations in the regulatory events that govern immune responsiveness in EOP. These alterations might contribute to increased susceptibility to disease in certain individuals. Although there are no numerical abnormalities in the proportions of T cells, T‐cell subsets, or B cells in the peripheral blood of EOP subjects, there may be alterations in the T helper‐T suppressor ratio within the actual lesions, and these may affect local B‐cell proliferation and function. Antibody produced against the antigens of pathogenic bacteria in EOP has a prominent IgG2 component but is now believed to be primarily protective to the host. Peripheral blood mononuclear cells from EOP patients have been reported to exhibit a reduced autologous mixed lymphocyte reaction, and a higher‐than‐normal response to B‐cell mitogens. Whether or not these phenomena are important in progression or resolution of EOP is unknown. Locally acting cytokines such as IL‐4 may be elevated, and this may influence the nature of the response. Use of molecular techniques to test possible relationships between susceptibility to EOP and the lymphocyte response, such as evaluation of MHC Class II and TCR gene usage, promises to provide further clues as to the role of lymphoid cells in, and genetic nature of, these forms of periodontitis. J Periodontol 1996;67:332–336.

show abstract

Impaired generation of high-affinity interleukin-2 receptors in the autologous mixed lymphocyte reaction in rheumatoid arthritis

Cited by 3 publications

References 19 publications

Effect of 5- Dihydrotestosterone on T-cell Proliferation of the Female Nonobese Diabetic Mouse

Effect of 5- Dihydrotestosterone on T-cell Proliferation of the Female Nonobese Diabetic Mouse

Ex Vivo Homeostatic Proliferation of CD4+ T Cells in Rheumatoid Arthritis Is Dysregulated and Driven by Membrane-Anchored TNFα

Lymphocyte Function in Early‐Onset Periodontitis

Contact Info

Product

Resources

About