EphB6-null mutation results in compromised T cell function
Hongyu Luo, … , Johanne Tremblay, Jiangping Wu
Hongyu Luo, … , Johanne Tremblay, Jiangping Wu
Published December 15, 2004
Citation Information: J Clin Invest. 2004;114(12):1762-1773. https://doi.org/10.1172/JCI21846.
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Article Immunology

EphB6-null mutation results in compromised T cell function

Abstract

So far, there is very limited knowledge about the role of Eph kinases, the largest family of receptor tyrosine kinases, in the immune system. Here, using EphB6–/– mice, we demonstrated that in vitro and in vivo T cell responses such as lymphokine secretion, proliferation, and the development of delayed-type skin hypersensitivity and experimental autoimmune encephalitis in EphB6–/– mice were compromised. On the other hand, humoral immune responses, such as serum levels of different Ig isotypes and IgG response to tetanus toxoid, were normal in these mice. Mechanistically, we showed that EphB6 migrated to the aggregated TCRs and rafts after TCR activation. Further downstream, in the absence of EphB6, ZAP-70 activation, LAT phosphorylation, the association of PLCγ1 with SLP-76, and p44/42 MAPK activation were diminished. Thus, we have shown that EphB6 is pivotal in T cell function.

Authors

Hongyu Luo, Guang Yu, Johanne Tremblay, Jiangping Wu

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EphB6 was essential for DTH and EAE, but not humoral immune response. (A...
EphB6 was essential for DTH and EAE, but not humoral immune response. (A) DTH against FITC was reduced in EphB6–/– mice. EphB6–/– mice (n = 9) and their WT littermates (n = 7) were assayed for DTH against FITC. The increase of ear thickness of each mouse is presented, and horizontal bars mark the median increase. The difference between the 2 groups was statistically significant (P < 0.05, 2-tailed Student’s t test). (B) Reduced severity of EAE development in EphB6–/– mice. EAE was induced in EphB6–/– mice (n = 14) and their WT littermates (n = 14), and its clinical manifestation was scored daily in a 2-way blind fashion. The percentage of mice in each group with severe EAE was plotted. From day 14 to day 35, the difference of disease severity in the 2 groups was statistically significant (P < 0.05, Mann-Whitney rank sum test). (C and D) Serum Ab isotype levels in EphB6–/– mice were similar to those in EphB6+/+ mice. Serum Ab isotypes, as indicated, of EphB6–/– and EphB6+/+ mice were measured by ELISA, and means ± SD are shown. There were no significant differences in the Ab isotype levels between EphB6+/+ and EphB6–/– mice (P > 0.05 for all the comparisons, Student’s t test). (E) No significant difference in anti-TT Ab production between EphB6–/– and EphB6+/+ mice. EphB6–/– mice (n = 8) and their WT littermates (n = 7) were immunized with TT, and their serum anti-TT Abs were measured at the indicated times by ELISA. The difference between the 2 groups was not significant (P > 0.05, 2-tailed Student’s t test).