Differential effect of L3T4+ cells on recovery from total-body irradiation.
We have examined the importance of L3T4+ (murine equivalent to CD4+) cells for hematopoietic regulation in vivo in unperturbed mice and mice recovering from total-body irradiation (TBI) using a cytotoxic monoclonal antibody (MoAb) raised with the GK 1.5 hybridoma. Ablating L3T4+ cells in "normal" (unperturbed) B6D2F1 mice substantially decreased the S-phase fraction (determined by in vivo hydroxyurea suicide) of erythroid progenitor cells (erythroid colony-forming units, CFU-E) as compared to the pretreatment level (10% +/- 14.1% [day 3 following depletion] vs 79.8% +/- 15.9%, respectively) with a corresponding decrease in the marrow content of CFU-E at this time to approximately 1% of the pretreatment value. Although the S-phase fraction of CFU-GM was decreased to 2.2% +/- 3.1% 3 days after L3T4+ cell ablation from the 21.3% +/- 8.3% pretreatment value, CFU-GM cellularity showed little change over the 3 days following anti-L3T4 treatment. Anti-L3T4 MoAb treatment had little or no effect on either the S-phase fraction or the marrow content of hematopoietic "stem cells" (spleen colony-forming units, CFU-S) committed to myeloerythroid differentiation. Ablating L3T4+ cells prior to a single dose of 2 Gy TBI resulted in significantly reduced marrow contents of CFU-S on day 3 and granulocyte-macrophage colony-forming units (CFU-GM) on day 6 following TBI, with little or no effect on the corresponding recovery of CFU-E. The present findings provide the first in vivo evidence that L3T4+ cells are involved in: 1) maintaining the proliferative activity of CFU-E and CFU-GM in unperturbed mice and 2) supporting the restoration of CFU-S and CFU-GM following TBI-induced myelosuppression.
Pantel
K
K
Wayne State University School of Medicine, Department of Internal Medicine, Detroit, MI 48201.
Nakeff
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001853:Bone Marrow / Q000528:radiation effects; D001854:Bone Marrow Cells; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D002452:Cell Count; D003602:Cytotoxicity, Immunologic; D015672:Erythroid Precursor Cells / Q000166:cytology; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000166:cytology; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology; D014916:Whole-Body Irradiation
D000911:Antibodies, Monoclonal