Mice homozygous for the viable motheaten (meυ) allele manifest abnormalities in
thymocytopoiesis, are severely immunodeficient, and develop autoimmune disorders
early in life. Premature thymic involution occurs in meυ/meυ mice, and their bone marrow
prothymocytes are unable to repopulate the thymus of adoptive recipients following
intravenous (i.v.) transfer. However, analysis of thymocytopoiesis following intrathymic
(i.t.) adoptive transfer of bone marrow from meυ/meυ mice demonstrates the presence of
normal numbers of prothymocytes. To investigate intrathymic development in meυ/meυ
mice, we determined intrathymic precursor cell number and activity. Dual labeling
analyses showed that an involuted meυ/meυ thymus is relatively enriched (fivefold) in
CD4– CD8– thymocytes (intrathymic precursor phenotype) compared with wild-type
(+/+) thymus. However, thymocytes from meυ/meυ mice were deficient in precursor
activity when adoptively transferred i.t. into irradiated recipients. Thymocytes
recovered from the involuted thymus of aged or steroid-treated normal mice also
displayed reduced precursor activity. However, the phenotypic profile of thymocyte
subsets from steroid-treated mice was enriched in single positive cells (mature
phenotype) and was distinctly different from the subset distribution of thymocytes in
meυ/meυ and aged mice. These results suggest that intrathymic precursor activity in
meυ/meυ mice is decreased, and may be reflective of decreased prothymocyte seeding to
the thymus in vivo, In addition, the results suggest that the thymic involution in meυ/meυ
mice is not due solely to effects of corticosteroids.