Neonatal adoptive transfer of lymphocytes rescues social behavior during adolescence in immune deficient mice

Abstract

Accumulating evidence has shown that adaptive immune cells are capable of modulating behavior and cognition via interactions with the brain and central nervous system elements. Nevertheless, since a vast majority of these studies were conducted in adult, constitutive knockout models of immune deficiency, it raises the question of whether compensatory mechanisms associated with development in a lymphopenic environment may explain some of the behavioral observations. To address this, neonate Rag2-/- (P2) mice were reconstituted with whole lymphocytes (ReconWL) derived from GFP+ wild type donors. Starting at 5 weeks of age (mid-adolescence) ReconWL, saline injected Rag2-/- and C57BL/6 J control mice underwent a series of behavioral tests including the open field, social interaction and sucrose preference tests. Then at 12 weeks (young adult) they were evaluated in the Morris Water Maze. Remarkably, reconstituted mice showed changes in almost all aspects that were assessed. Perhaps most notable however, was the complete rescue of impaired social behavior displayed by non-reconstituted Rag2-/- mice. While Rag2-/- mice preferred a non-social area and spent significantly less time with a conspecific mouse, ReconWL mice were comparable to wild type mice. Additionally, consistent with previous reports, Rag2-/- mice had deficits in reversal learning in the MWM that were rescued by reconstitution. These findings support a role for lymphocytes in modulating a spectrum of behavioral and cognitive processes across the lifespan.