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Stem cell recovery from cyclophosphamide‐induced myelosuppression requires the presence of CD4 + cells
Author(s) -
Pantel Klaus,
And Zora Djuric,
Nakeff Alexander
Publication year - 1990
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1990.tb02644.x
Subject(s) - cyclophosphamide , cytotoxicity , cytotoxic t cell , haematopoiesis , in vivo , monoclonal antibody , cell culture , chemistry , microbiology and biotechnology , medicine , stem cell , immunology , in vitro , pharmacology , andrology , endocrinology , biology , antibody , chemotherapy , biochemistry , genetics
Summary Recently, we have reviewed studies regarding the growth‐stimulating effect of CD4 + cells on haematopoietic cells in culture (Pantel & Nakeff, 1989a). In the present study we have tested the physiologic relevance of this interaction using a drug‐perturbed mouse model. The long‐term application of cyclophosphamide (CY, 30 mg/kg/d, five i.p. injections per week over 7 weeks) in B6D2F1 mice resulted in initial CY‐induced cytotoxicity to CFU‐S followed by the re‐establishment to pretreatment values of the femoral content of CFU‐S within 2–3 weeks of CY‐treatment. An examination of CY‐metabolism in these treated mice excluded a pharmacological explanation for the compensation of CY‐cytotoxicity. However, a three‐fold increase in the cycling fraction of CFU‐S (determined by in vivo hydroxyurea suicide) was observed concomitant with a two‐fold increase in the femoral content of L3T4 + cells (the murine equivalent to human CD4 + cells), as compared to the corresponding values in untreated mice. Ablating these L3T4 + cells in vivo by means of a cytotoxic monoclonal antibody (MoAb) to the L3T4 determinant resulted in a decrease in the cycling fraction of CFU‐S from 56.8% to essentially zero and a decrease in the femoral content of CFU‐S when comparing mice receiving either CY alone or CY plus MoAb, respectively. It would appear that the CY‐induced increase in the proliferative activity of CFU‐S requires the presence of L3T4 + cells. These data constitute the first in situ evidence for the physiologic relevance of immunocompetent L3T4 + cells as regulators involved in the recovery of stem cells from drug‐induced myelosuppression.