Human invariant NKT cells are required for effective in vitro alloresponses

Scott Patterson, Ioannis Kotsianidis, António Almeida, Marianna Politou, Amin Rahemtulla, Bini Matthew, Richard R. Schmidt, Vincenzo Cerundolo, Irene A.G. Roberts, Anastasios Karadimitris*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


NKT cells are a small subset of regulatory T cells conserved in humans and mice. In humans they express the Vα24Jα18 invariant chain (hence invariant NKT (iNKT) cells) and are restricted by the glycolipid-presenting molecule CD1d. In mice, iNKT cells may enhance or inhibit anti-infectious and antitumor T cell responses but suppress autoimmune and alloreactive responses. We postulated that iNKT cells might also modulate human alloreactive responses. Using MLR assays we demonstrate that in the presence of the CD1d-presented glycolipid α-galactosylceramide (αGC) alloreactivity is enhanced (37 ± 12%; p < 0.001) in an iNKT cell-dependent manner. iNKT cells are activated early during the course of the MLR, presumably by natural ligands. In MLR performed without exogenous ligands, depletion of iNKT cells significantly diminished the alloresponse in terms of proliferation (58.8 ± 24%; p < 0.001) and IFN-γ secretion (43.2 ± 15.2%; p < 0.001). Importantly, adding back fresh iNKT cells restored the reactivity of iNKT cell-depleted MLR to near baseline levels. CD1d-blocking mAbs equally reduced the reactivity of the iNKT cell-replete and -depleted MLR compared with IgG control, indicating that the effect of iNKT cells in the in vitro alloresponse is CD1d-dependent. These findings suggest that human iNKT cells, although not essential for its development, can enhance the alloreactive response.

Original languageEnglish
Pages (from-to)5087-5094
Number of pages8
JournalJournal of Immunology
Issue number8
Publication statusPublished - 15 Oct 2005
Externally publishedYes


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