Homing And In-Situ Differentiation Of Resident Pulmonary Lymphocytes

At birth, T lymphocytes which colonize the lung are mainly of the gamma delta subset, while alpha beta T cells predominate in the spleen. Thus, 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 age, from a predominance of V(gamma)6 at birth to a predominance of V(gamma)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 population present at birth is replaced by V(gamma)4 T cells. In the postnatal period, both RAG-1 and RAG-2 genes are expressed at high levels in the RPL population. TCR bearing cells are among those that express RAG genes, indicating that maturation of T cells takes place in this organ. In addition, transfer experiments reveal that lymphoid precursors are present in the lung. The stage of differentiation of these precursors will be characterized in future studies. The data presented here indicate that pulmonary T lymphocytes are derived from both migrants of thymic origin and from precursors which have undergone differentiation 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 are typical for the pulmonary environment.