Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1974 Jun 1;139(6):1529–1539. doi: 10.1084/jem.139.6.1529

POTENTIATION OF T-CELL-MEDIATED IMMUNITY BY SELECTIVE SUPPRESSION OF ANTIBODY FORMATION WITH CYCLOPHOSPHAMIDE

P H Lagrange 1, G B Mackaness 1, T E Miller 1
PMCID: PMC2139678  PMID: 4598017

Abstract

Delayed-type hypersensitivity (DTH) appears in mice immunized with less than an optimal immunogenic dose of sheep red blood cells (SRBC), but is blocked progressively as antibody production increases in response to larger doses of SRBC. Treatment with cyclophosphamide (CY) was shown to release T cells from this inhibitory influence of the humoral response, and cause enhancement of DTH. The magnitude of this enhancing effect on T-cell activity was markedly dependent on the time of treatment relative to the time of immunization, and on the time chosen for measuring DTH. The reasons for these pronounced effects of timing are threefold: (a) CY given before antigenic stimulation has a long-lasting effect on antibody formation, but no apparent effect on the precursors of activated T cells. (b) After antigenic stimulation, T cells also become susceptible to CY. (c) The production of a nonspecific participant (monocyte) in the DTH reaction is also suppressed by CY, though the supply of circulating monocytes is not immediately affected by the drug. The differential effect of CY on T and B lymphocytes depends on the differing physiological states of the majority of cells that make up these two populations. The former are resting cells that are insensitive to CY until exposed to specific antigen, while the latter are drawn from a rapidly replicating precursor pool and are susceptible to CY at all times.

Full Text

The Full Text of this article is available as a PDF (573.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. DeWys W. D., Kight N. Kinetics of cyclophosphamide damage--sublethal damage repair and cell-cycle-related sensitivity. Mod Hosp. 1969 Jan;112(1):155–163. [PubMed] [Google Scholar]
  2. Kettman J. Delayed hypersensitivity: is the same population of thymus-derived cells responsible for cellular immunity reactions and the carrier effect? Immunol Commun. 1972;1(3):289–299. doi: 10.3109/08820137209022942. [DOI] [PubMed] [Google Scholar]
  3. Lagrange P. H., Mackaness G. B., Miller T. E. Influence of dose and route of antigen injection on the immunological induction of T cells. J Exp Med. 1974 Mar 1;139(3):528–542. doi: 10.1084/jem.139.3.528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Lerman S. P., Weidanz W. P. The effect of cyclophosphamide on the ontogeny of the humoral immune response in chickens. J Immunol. 1970 Sep;105(3):614–619. [PubMed] [Google Scholar]
  5. Mackaness G. B., Auclair D. J., Lagrange P. H. Immunopotentiation with BCG. I. Immune response to different strains and preparations. J Natl Cancer Inst. 1973 Nov;51(5):1655–1667. doi: 10.1093/jnci/51.5.1655. [DOI] [PubMed] [Google Scholar]
  6. Mackaness G. B., Lagrange P. H., Miller T. E., Ishibashi T. Feedback inhibition of specifically sensitized lymphocytes. J Exp Med. 1974 Mar 1;139(3):543–559. doi: 10.1084/jem.139.3.543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Mackaness G. B. The influence of immunologically committed lymphoid cells on macrophage activity in vivo. J Exp Med. 1969 May 1;129(5):973–992. doi: 10.1084/jem.129.5.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. McGregor D. D., Koster F. T. The mediator of cellular immunity. IV. Cooperation between lymphocytes and mononuclear phagocytes. Cell Immunol. 1971 Aug;2(4):317–325. doi: 10.1016/0008-8749(71)90066-9. [DOI] [PubMed] [Google Scholar]
  9. Miller T. E., Mackaness G. B., Lagrange P. H. Immunopotentiation with BCG. II. Modulation of the response to sheep red blood cells. J Natl Cancer Inst. 1973 Nov;51(5):1669–1676. doi: 10.1093/jnci/51.5.1669. [DOI] [PubMed] [Google Scholar]
  10. NOSSAL G. J., MAKELA O. Autoradiographic studies on the immune response.I. The kinetics of plasma cell proliferation. J Exp Med. 1962 Jan 1;115:209–230. doi: 10.1084/jem.115.1.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Röpke C., Everett N. B. Small lymphocyte populations in the mouse bone marrow. Cell Tissue Kinet. 1973 Sep;6(5):499–507. doi: 10.1111/j.1365-2184.1973.tb01637.x. [DOI] [PubMed] [Google Scholar]
  12. SANTOS G. W., OWENS A. H., Jr A COMPARISON OF THE EFFECTS OF SELECTED CYTOTOXIC AGENTS ON ALLOGENEIC SKIN GRAFT SURVIVAL IN RATS. Bull Johns Hopkins Hosp. 1965 May;116:327–340. [PubMed] [Google Scholar]
  13. Santos G. W. Symposium on immunosuppressive drugs. Immunosuppressive drugs. I. Fed Proc. 1967 May-Jun;26(3):907–913. [PubMed] [Google Scholar]
  14. Stockman G. D., Heim L. R., South M. A., Trentin J. J. Differential effects of cyclophosphamide on the B and T cell compartments of adult mice. J Immunol. 1973 Jan;110(1):277–282. [PubMed] [Google Scholar]
  15. Strober S. Initiation of antibody responses by different classes of lymphocytes. V. Fundamental changes in the physiological characteristics of virgin thymus-independent ("B") lymphocytes and "B" memory cells. J Exp Med. 1972 Oct 1;136(4):851–871. doi: 10.1084/jem.136.4.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Turk J. L., Parker D. Further studies on B-lymphocyte suppression in delayed hypersensitivity, indicating a possible mechanism for Jones-Mote hypersensitivity. Immunology. 1973 Apr;24(4):751–758. [PMC free article] [PubMed] [Google Scholar]
  17. Turk J. L., Parker D., Poulter L. W. Functional aspects of the selective depletion of lymphoid tissue by cyclophosphamide. Immunology. 1972 Oct;23(4):493–501. [PMC free article] [PubMed] [Google Scholar]
  18. Uhr J. W. Delayed hypersensitivity. Physiol Rev. 1966 Jul;46(3):359–419. doi: 10.1152/physrev.1966.46.3.359. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES