Cytotoxicity of fresh NK1.1+ T cell receptor alpha/beta+ thymocytes against a CD4+8+ thymocyte population associated with intact Fas antigen expression on the target.

Abstract

SummaryRecent studies have revealed that 10-20% of CD4+8 -or CD4-8-thymocyte populations contain NKI.1 + T cell receptor (TCR)-cff~ + cells. This subpopulation shows characteristics that are different from NKI.1-CD4 § or NKI.1-CD8 + T calls and seems to have developed in a manner different from NKI.1-T cells. Although extensive studies have been performed on the NKI.1 + TCR-od~8 + thymocytes, the physiological role of the NKI.1 + TCR-c~/~/+ thymocytes has been totally unclear. In the present study, we found that fleshly isolated NKI.1 + TCR-odB + thymocytes, but neither whole thymocytes nor lymph node T cells, directly killed CD4 +8 § thymocytes from normal syngeneic or allogeneic mice by using a long-term cytotoxic assay in which flow cytometry was used to detect the cytotoxidty. However, only weak cytotoxicity was detected against thymocytes from lpr mice on which the Fas antigen that transduces signals for apoptosis into the cells is not expressed. Furthermore, the NKI.1 + TCR-ot/B + thymocytes exhibited high cytotoxicity against T lymphoma targets transfected withj~s genes as compared with the parental T lymphoma targets or target cells transfected with mutatedJas genes, which lack the function of transducing signals. On the other hand, NKI.1 § effector thymocytes from gld mice that carry a point mutation in Fas ligand did not kill thymocyte targets from normal mice. The present findings, thus, consistently suggest that the NKI.1 + TCR-ot/~8 + thymocytes kill a subpopulation among CD4+8 + thymocytes via Fas antigen and in this way regulate generation of T lineage cells in the thymus.

Natural killer T cells ameliorate antibody-induced arthritis in macrophage migration inhibitory factor transgenic mice

“…Similar findings have been reported by Singh et al (26,36). However, since differences in cytokine levels between ·-GalCer-and vehicle-treated MIF Tg mice were modest, it is likely that mechanisms other than a shift in the cytokine response (e.g., direct cell-to-cell interactions) may be involved in the NKT cell-mediated regulation of arthritis (41).…”

A naturally occurring soluble isoform of murine Fas generated by alternative splicing.

“…3 /3). We conclude that the recently reported exquisite sensitivity of CD4+CD8 + thymocytes to apoptosis induced by Fas ligation (27)(28)(29) is not caused by differential low expression of Fas B in these cells. In contrast to thymocytes, there is a strong case that Fas is important in the apoptosis of mature T cells and that this apoptosis occurs in the liver (4, 31).…”

“…Two T cell populations, thymocytes and IHLs, were selected for detailed analysis. Thymocyte subsets were tested because thymocytes are Fas positive (16,23), highly susceptible to apoptosis (24)(25)(26), and differentially susceptible to Fas-mediated apoptosis (27)(28)(29). Thymocytes were sorted by FACS | into subsets at different developmental stages based on TCR expression or CD4 and CD8 phenotype.…”

Exacerbated Susceptibility to Infection-Stimulated Immunopathology in CD1d-Deficient Mice

“…CD1d-restricted cells can be directly cytolytic to some targets via perforin-dependent or granzyme-dependent mechanisms (59,80) and therefore may possess antiparasite effector functions. The trend toward higher parasite numbers we observed in the ileums of CD1d-infected mice (Table I) is consistent with impaired antiparasite effector functions in CD1d-deficient mice.…”