Is autoimmunity a side-effect of interleukin 2 production?

Krämer, Guido; Schauenstein, Konrad; Wick, Georg

doi:10.1016/0167-5699(86)90102-7

Cited by 22 publications

(2 citation statements)

References 40 publications

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“…Although the precise triggering events that initiate autoimmune diseases, including IDDM, are unknown, there is evidence to support the hypothesis that lymphoid cells responsive to IL-2 are important as autoimmune effectors (26). Similarly, our findings suggest that IL-2-dependent lymphoid cells may mediate islet fi-cell destruction in the BB/W diabetic rat.…”

Section: Discussionmentioning

confidence: 55%

Interleukin 2 Activates BB/W Diabetic Rat Lymphoid Cells Cytotoxic to Islet Cells

1987

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We compared the cytotoxic effects to islet cells of lymphoid cells from diabetic and diabetes-resistant (DR) BioBreeding/Worcester (BB/W) rats with a 51Cr-release assay to detect lysis of normal rat islet cells. Splenic lymphoid cells from diabetic rats were more cytotoxic to islet cells (11.3 +/- 3.8%) than were lymphoid cells from DR rats (4.0 +/- 2.6%). This difference was amplified by incubating the lymphoid cells for 20 h with 5 micrograms/ml concanavalin A (ConA); islet cell lysis was 39.3 +/- 4.5% by ConA-activated diabetic cells and 9.6 +/- 2.7% by ConA-activated DR cells. The cytotoxic lymphoid cells were identified as natural killer (NK) cells, because treatment of diabetic lymphoid cells with anti-asialo GM1 serum and complement selectively removed a monoclonal antibody-defined subset of NK cells (OX8 +), and the NK-depleted lymphoid cells were not cytotoxic to either islet or NK-sensitive YAC-1 cells, even after culture with ConA. Of several lymphokine products of ConA-stimulated lymphoid cells, interleukin 2 (IL-2), but not interleukin 1 or interferon-gamma, significantly activated splenic lymphoid cells cytotoxic to islet cells, and the lymphoid cells from diabetic rats were more sensitive to IL-2 (3 U/ml) than were the cells from DR rats (30 U/ml). This study reveals the presence of ConA- and IL-2-responsive islet cytotoxic NK cells in the diabetic BB/W rat and suggests that IL-2 activation of NK cells may contribute to islet beta-cell destruction and diabetes in this animal.

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Section: Discussionmentioning

confidence: 55%

Interleukin 2 Activates BB/W Diabetic Rat Lymphoid Cells Cytotoxic to Islet Cells

1987

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“…Lastly, using limiting dilution analysis, Hefeneider et al [lo] reported that the total number of IL 2-producing cells present in the spleens of MRL-lprllpr mice may actually exceed that present in those of immunologically normal mice. Based on this body of literature, Kromer and colleagues [34] postulated that hypersecretion of IL2 in vivo may be instrumental in triggering autoimmunity.…”

Section: Discussionmentioning

confidence: 98%

The role of L3T4⁺ cells in the pathogenesis of lupus in lpr‐bearing mice. I. Defects in the production of interleukins 2 and 3

et al. 1987

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Mice which bear the lpr gene spontaneously develop autoimmune syndromes characterized by massive expansion of an unusual T cell subset which is phenotypically Thy-1+, L3T4-, Lyt-2-, B220+. The mutant T cells are refractory to stimulation with mitogenic lectins and, by implication, are thought to be solely responsible for the defects in lymphokine production manifested by lpr mice. The contribution of the remaining L3T4+ T cell subset to the latter derangements has not been previously examined and is the focus of this study. We found that abnormalities in concanavalin A-induced interleukin 2 and 3 production in the spleens of MRL-lpr/lpr and C57BL/6.lpr mice occurred in the presence of limited infiltration with B220+, L3T4- T cells. Mixing experiments indicated that B220+ T cells were not suppressive. Furthermore, lpr spleen cells enriched for L3T4+ cells and depleted of sIg+, B220+ and Lyt-2+ cells demonstrated reductions in lymphokine production which were comparable to those seen in unfractionated preparations. Spleen cells from C57BL/6.lpr mice, enriched for L3T4+ cells, were also markedly impaired in a mixed leukocyte reaction in response to stimulator cells from the class II major histocompatibility complex mutant bm12. The results indicate that the aberrations in lymphokine production and proliferation in the spleen cells of lpr mice involve not only B220+ T cells but also L3T4+ cells and suggest a potential role for the L3T4+ subset in the pathogenesis of lupus in lpr-bearing mice.

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Enhanced CD3‐mediated T lymphocyte proliferation in patients with systemic lupus erythematosus

Stekman¹,

Blasini²,

Leon‐Ponte³

et al. 1991

Arthritis & Rheumatism

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Nonfractionated peripheral blood lymphocytes from patients with systemic lupus erythematosus (SLE) showed enhanced proliferative responses when stimulated via the CD3 pathway. In contrast, proliferative responses induced by phytohemagglutinin were diminished in SLE patients. Levels of CD3-induced interleukin-2 production and interleukin-2 receptor expression were comparable with normal levels. Highly purified T cells also showed augmented CD3 responses, but only in the presence of phorbol myristate acetate or a combination of phorbol myristate acetate plus calcium ionophore A23187, and not with calcium ionophore alone. The data suggest integrity of the T cell receptorKD3 pathway for T cell activation in patients with SLE, as examined in cultures stimulated with specific anti-CD3 monoclonal antibodies rather than with multivalent lectins. An increased response via the CD3 complex could contribute to the autoimmune activity in human SLE.

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Is autoimmunity a side-effect of interleukin 2 production?

Cited by 22 publications

References 40 publications

Interleukin 2 Activates BB/W Diabetic Rat Lymphoid Cells Cytotoxic to Islet Cells

Interleukin 2 Activates BB/W Diabetic Rat Lymphoid Cells Cytotoxic to Islet Cells

The role of L3T4⁺ cells in the pathogenesis of lupus in lpr‐bearing mice. I. Defects in the production of interleukins 2 and 3

Enhanced CD3‐mediated T lymphocyte proliferation in patients with systemic lupus erythematosus

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Is autoimmunity a side-effect of interleukin 2 production?

Cited by 22 publications

References 40 publications

Interleukin 2 Activates BB/W Diabetic Rat Lymphoid Cells Cytotoxic to Islet Cells

Interleukin 2 Activates BB/W Diabetic Rat Lymphoid Cells Cytotoxic to Islet Cells

The role of L3T4+ cells in the pathogenesis of lupus in lpr‐bearing mice. I. Defects in the production of interleukins 2 and 3

Enhanced CD3‐mediated T lymphocyte proliferation in patients with systemic lupus erythematosus

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The role of L3T4⁺ cells in the pathogenesis of lupus in lpr‐bearing mice. I. Defects in the production of interleukins 2 and 3