HOMING AND IN-SITU DIFFERENTIATION OF RESIDENT PULMONARY LYMPHOCYTES

At birth, T lymphocytes which colonize the lung are mainly of the gamm a delta subset, while alpha beta T cells predominate in the spleen. Th us, the lung is a preferred site for the homing of gamma delta T cells in the perinatal period. However, after birth, the pattern of V-gamma gene usage among resident pulmonary lymphocytes (RPL) changes with ag e, from a predominance of V(gamma)6 at birth to a predominance of V(ga mma)4 in older mice. The generation of the V(gamma)6 fraction appears to be thymus dependent, since in athymic nude mice, the V(gamma)6 popu lation present at birth is replaced by V(gamma)4 T cells. In the postn atal period, both RAG-1 and RAG-2 genes are expressed at high levels i n the RPL population. TCR bearing cells are among those that express R AG genes, indicating that maturation of T cells takes place in this or gan. In addition, transfer experiments reveal that lymphoid precursors are present in the lung. The stage of differentiation of these precur sors will be characterized in future studies. The data presented here indicate that pulmonary T lymphocytes are derived from both migrants o f thymic origin and from precursors which have undergone differentiati on and selection in the lung. The population that is generated in situ and that has not been selected in the thymus may include cells that a re typical for the pulmonary environment.