The origin and development of the lymphocyte populations of the thymus and the lymph nodes have been studied in the fetal cat. Fetuses ranging in age from 25 days (16 mm) to 50 days (98 mm) of gestation have been examined following formol-sublimate-acetic acid fixation, parlodion-paraffin embedding and subsequent staining with toluidine blue, hematoxylin-eosin and periodic acid-Schiff methods.

These studies have shown an occasional lymphocyte in the primitive lymph nodes as early as the thirtieth day of gestation. A number of small- and medium-sized lymphocytes are scattered randomly in the mesenchymal condensation of the developing lymph nodes by 33 days. Lymphocyte proliferation proceeds relatively slowly, and morphological evidence suggests that lymphocytes appear to develop from the mesenchymal or reticular cells of the developing lymph nodes without the intermediate formation of lymphoblasts. In the thymus, the first lymphocytic cells formed are lymphoblasts. These cells appear initially between 31 and 33 days. Lymphoblastic transformation is not generalized until the thirty-fifth day; at this time, an occasional medium-sized lymphocyte is evident and vascularization of the thymus begins. Development proceeds rapidly and the thymus is filled with medium-sized and small lymphocytes by 40 days. At this time, large clusters of small lymphocytes are evident in the capsular connective tissue, and these cells soon enter lymphatic vessels located in the capsular connective tissue.

These observations indicate that the initial appearance of lymphocytes in lymph nodes precedes the appearance of lymphocytic precursors (lymphoblasts) in the thymus by 1–2 days and the development of lymphocytes in the thymus by approximately five days. Therefore, the early lymphocyte population in the lymph nodes is not dependent upon the dissemination of thymic lymphocytes or their precursors. Thymic lymphocytes, however, may contribute to the lymphocyte population of the lymph nodes at later stages of fetal development, after vascularization of the thymus and after the formation of lymphatic vessels in the capsule.