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

Abstract

Accumulating evidence has shown that lymphocytes modulate behavior and cognition by direct interactions with the central nervous system. Studies have shown that reconstitution by adoptive transfer of lymphocytes from wild type into immune deficient mice restores a number of neurobehavioral deficits observed in these models. Moreover, it has been shown that these effects are mostly mediated by T lymphocytes. Studies of adoptive transfer thus far have employed adult mice, but whether lymphocytes may also modulate behavior during development remains unknown. In the present study, neonate lymphocyte deficient Rag2^-/- mice were reconstituted within 48 hours after birth with lymphoid cells from transgenic donors expressing green fluorescent protein, allowing for their identification in various tissues in recipient mice while retaining all functional aspects. Adolescent Rag2^-/- and reconstituted Rag2^-/- along with C57BL/6J WT mice underwent a series of behavioral tests, including open field, social interaction and sucrose preference tests. At 12 weeks they were evaluated in the Morris Water Maze (MWM). Reconstituted mice showed changes in almost all aspects of behavior that were assessed, with a remarkable complete rescue of impaired social behavior displayed by adolescent Rag2^-/- mice. Consistent with previous reports in adult mice, neonatal reconstitution in Rag2^-/- mice restored spatial memory in the MWM. The presence of donor lymphocytes in the brain of neonatally reconstituted Rag2^-/- mice was confirmed at various developmental points. These findings provide evidence that lymphocytes colonize the brain during postnatal development and modulate behavior across the lifespan supporting a role for adaptive immunity during brain maturation.

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