Requirement of Gαi in thymic homing and early T cell development

Demonstration of thymic homing dependent on Gαi proteins is one of the keys to determine whether thymic entrance of blood-borne progenitors is a highly selective process. The present study provides compelling evidence of an indispensable role for Gαi proteins in this process. Absence of either Gαi2 or Gαi3 significantly abrogated thymic homing, with an effect of Gαi3 being greater than that of Gαi2. Pertussis toxin treatment that blocks both Gαi2 and Gαi3 almost completely blocked thymic seeding in the thymus. Null mutation of Gαi3 also hindered bone marrow cell development and thus reduced production of pre-thymic progenitors. In contrast, Gαi2 exhibited a more prominent role than Gαi3 in guidance of CD4−CD8− double negative (DN) 1 cell migration and early thymic differentiation. The Gαi-deficiency-induced defects might be compensated for in part via augmented function of thymic stromal cells so that a nearly normal output of mature T cells could be maintained in these Gαi-deficient mice. These studies underscore the importance of Gαi in regulating thymic homing and pre-thymic and early thymocyte differentiation.