Requirement of Galphai in thymic homing and early T cell development.

Demonstration of thymic homing dependent on Galphai 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 Galphai proteins in this process. Absence of either Galphai2 or Galphai3 significantly abrogated thymic homing, with an effect of Galphai3 being greater than that of Galphai2. Pertussis toxin treatment that blocks both Galphai2 and Galphai3 almost completely blocked thymic seeding in the thymus. Null mutation of Galphai3 also hindered bone marrow cell development and thus reduced production of pre-thymic progenitors. In contrast, Galphai2 exhibited a more prominent role than Galphai3 in guidance of CD4-CD8--double negative (DN) 1 cell migration and early thymic differentiation. The Galphai-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 Galphai-deficient mice. These studies underscore the importance of Galphai in regulating thymic homing and pre-thymic and early thymocyte differentiation.