2009
DOI: 10.1016/j.autrev.2008.07.045
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Therapeutic potential of CD8+ cytotoxic T lymphocytes in SLE

Abstract: Recent evidence supports the idea that following a break in tolerance, CD8 cytotoxic T lymphocytes (CTL) may be an important but unrecognized mechanism for limiting expansion of autoreactive B cells. Failure of this mechanism could allow persistence of CD4 T cell driven polyclonal B cell activation resulting in clinical lupus. Although CD8 CTL failure may occur early in disease, work in mice supports the concept that therapeutic CTL enhancement may be both practical and beneficial in lupus. Devising such thera… Show more

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Cited by 37 publications
(32 citation statements)
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References 39 publications
(34 reference statements)
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“…Another possibility is that TNF-related apoptosis inducing ligand (TRAIL) produced by CTLs in the presence of IL-2 may induce DN T cell apoptosis. Given that CD8 + T cell function is impaired in both human and lupus-prone mice (51), IL-2 may restore CTL function that contributes to the elimination of pathogenic lymphocytes including DN T cells in MRL/ lpr mice. Taken together, our results suggest that CTLs treated with IL-2 can affect the pathogenic DN T cell viability and expansion.…”
Section: Discussionmentioning
confidence: 99%
“…Another possibility is that TNF-related apoptosis inducing ligand (TRAIL) produced by CTLs in the presence of IL-2 may induce DN T cell apoptosis. Given that CD8 + T cell function is impaired in both human and lupus-prone mice (51), IL-2 may restore CTL function that contributes to the elimination of pathogenic lymphocytes including DN T cells in MRL/ lpr mice. Taken together, our results suggest that CTLs treated with IL-2 can affect the pathogenic DN T cell viability and expansion.…”
Section: Discussionmentioning
confidence: 99%
“…4A, columns 1 & 3 respectively) consistent with a failure of DBA CD8 CTL maturation. These positive controls for acute and chronic GVHD phenotype demonstrate that: a) purification and recombination of CD4 and CD8 T cell subsets does not alter the expected two week phenotypes observed in unfractionated donor splenocyte transfer experiments (35), and b) T cells are necessary and sufficient for GVHD induction.…”
Section: Resultsmentioning
confidence: 88%
“…Comparing day 14 host B cell numbers, control matched B10.D2 CD4 + B10.D2 CD8 (matched B10.D2→F1) donor cells induce significant and profound host B cell elimination compared to uninjected F1 mice (Fig. 4A, columns 1 & 2 from the left) typical of an acute GVHD cytotoxic phenotype and indicative of a strong B10.D2 CD8 CTL response (35). In contrast, matched DBA CD4 and DBA CD8 donor T cells (matched DBA→F1) induce significant host B cell expansion typical of the expected day 14 stimulatory chronic GVHD (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…B cells are activated, expanded, and initially produce anti-ssDNA ab. Because host splenocytes are significantly reduced in acute GVHD and increased in chronic GVHD at 2 weeks, the 2-week phenotypes have been designated as cytotoxic and stimulatory, respectively [33]. …”
Section: Insights Into Lupus-associated Ctl and Il-2 Defects From Thementioning
confidence: 99%