Hematopoietic changes induced by a single injection of anti-CD3 monoclonal antibody into normal mice.
The present study evaluates hematopoietic modifications consecutive to in vivo treatment of mice with anti-CD3 monoclonal antibodies (mAb). The hamster mAb 145-2C11, administered in a single i.v. injection of 10 micrograms, induced the release of both interleukin 3 (IL-3) and GM-CSF into the circulation. IL-3 could be detected in the serum within 1 h, attained maximal levels after 4 h and had disappeared after 24 h. Three days later, treated mice exhibited a two- to threefold rise in blood neutrophil levels and increased spleen cell counts. Concomitantly, the incidence of nucleated erythroid cells in these spleens increased around 10-fold, relative to controls having received hamster Ig. At the same time point, clonogenic progenitor frequencies were 10-fold higher in spleens from treated mice than in those from control mice. Furthermore, the responsiveness of these splenocytes to IL-3, in terms of histamine synthesis, was enhanced. In contrast, bone marrow cell populations were only slightly affected by anti-CD3 injection. All hematopoietic changes required multivalent crosslinking of the mAb for induction, since F(ab')2 fragments lacked this activity. A return to normal occurred 7-10 days after treatment. Two i.v. injections of recombinant murine IL-3 together with recombinant murine GM-CSF on a single day had a less pronounced effect on progenitor cell frequencies in the spleen than treatment with anti-CD3. This difference is probably due to the amplification of growth factor-induced hematopoiesis by the interaction with other cytokines generated in response to anti-CD3.
Schneider
E
E
Université René Descartes-Paris V, CNRS URA 1461, Hôpital Necker, Paris, France.
Salaün
V
V
Ben Amor
A
A
Dy
M
M
D000818:Animals; D001854:Bone Marrow Cells; D017252:CD3 Complex / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects / Q000276:immunology*; D007275:Injections, Intravenous; D007377:Interleukin-3 / Q000096:biosynthesis / Q000378:metabolism; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016853:Muromonab-CD3 / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology
D017252:CD3 Complex; D007377:Interleukin-3; D016853:Muromonab-CD3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor