TY - JOUR
T1 - Tetraspanin CD37 contributes to the initiation of cellular immunity by promoting dendritic cell migration
AU - Gartlan, Kate
AU - Wee, Janet Lye-Keng
AU - Demaria, Maria
AU - Nastovska, Roza
AU - Chang, Tsz Man (Fiona)
AU - Jones, Eleanor
AU - Apostolopoulos, Vasso
AU - Pietersz, Geoffrey A
AU - Hickey, Michael John
AU - van Spriel, Annemiek B
AU - Wright, Mark Dexter
PY - 2013
Y1 - 2013
N2 - Previous studies on the role of the tetraspanin CD37 in cellular immunity appear contradictory. In vitro approaches indicate a negative regulatory role, whereas in vivo studies suggest that CD37 is necessary for optimal cellular responses. To resolve this discrepancy, we studied the adaptive cellular immune responses of CD37-/- mice to intradermal challenge with either tumors or model antigens and found that CD37 is essential for optimal cell-mediated immunity. We provide evidence that an increased susceptibility to tumors observed in CD37-/- mice coincides with a striking failure to induce antigen-specific IFN-gamma-secreting T cells. We also show that CD37 ablation impairs several aspects of DC function including: in vivo migration from skin to draining lymph nodes; chemo-tactic migration; integrin-mediated adhesion under flow; the ability to spread and form actin protrusions and in vivo priming of adoptively transferred naive T cells. In addition, multiphoton microscopy-based assessment of dermal DC migration demonstrated a reduced rate of migration and increased randomness of DC migration in CD37-/- mice. Together, these studies are consistent with a model in which the cellular defect that underlies poor cellular immune induction in CD37-/- mice is impaired DC migration.
AB - Previous studies on the role of the tetraspanin CD37 in cellular immunity appear contradictory. In vitro approaches indicate a negative regulatory role, whereas in vivo studies suggest that CD37 is necessary for optimal cellular responses. To resolve this discrepancy, we studied the adaptive cellular immune responses of CD37-/- mice to intradermal challenge with either tumors or model antigens and found that CD37 is essential for optimal cell-mediated immunity. We provide evidence that an increased susceptibility to tumors observed in CD37-/- mice coincides with a striking failure to induce antigen-specific IFN-gamma-secreting T cells. We also show that CD37 ablation impairs several aspects of DC function including: in vivo migration from skin to draining lymph nodes; chemo-tactic migration; integrin-mediated adhesion under flow; the ability to spread and form actin protrusions and in vivo priming of adoptively transferred naive T cells. In addition, multiphoton microscopy-based assessment of dermal DC migration demonstrated a reduced rate of migration and increased randomness of DC migration in CD37-/- mice. Together, these studies are consistent with a model in which the cellular defect that underlies poor cellular immune induction in CD37-/- mice is impaired DC migration.
UR - http://www.ncbi.nlm.nih.gov/pubmed/23420539
U2 - 10.1002/eji.201242730
DO - 10.1002/eji.201242730
M3 - Article
SN - 0014-2980
VL - 43
SP - 1208
EP - 1219
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 5
ER -