Elsevier

Cellular Immunology

Volume 125, Issue 1, January 1990, Pages 210-224
Cellular Immunology

Comparative analysis of splenic cell proliferation induced by interleukin 3 and by syngeneic accessory cells (syngeneic mixed leukocyte reaction): Evidence that autoreactive T-cell functioning instructs hematopoietic phenomena

https://doi.org/10.1016/0008-8749(90)90075-3Get rights and content

Abstract

Murine syngeneic mixed leukocyte reaction (SMLR) was studied under totally autologous culture conditions using syngeneic normal mouse serum in the culture. SMLR was detected in splenic, but not in lymph node, nonadherent responding cell populations (NWNAC). In the absence of stimulator, accessory cells (AC), IL3-containing fluids also induced splenic, but not lymph node, NWNAC growth. SMLR-derived supernatants contained IL3, but not IL2, activity, and production of this IL3 activity could be prevented by adding anti-CD4 mAbs to SMLR cultures. Precursor frequencies of both SMLR and IL3 splenic responses were very low and similar, and there was a synergism between IL3 and AC in induction of NWNAC growth. Growth of responding NWNAC was further enhanced by T-cell depletion with anti-Thy1 mAb and complement. Lack of T-cell proliferation in the SMLR was confirmed by BUdR and light protection experiments. Autoradiographs indicated that the same cell type grew in both SMLR and IL3-induced NWNAC cultures. Besides blast cells, cells with the appearance of immature monocytes with 3H-labeled nuclei were found in both kinds of culture. No labeled lymphocytes could be found. Both SMLR and IL3-induced NWNAC cultures contained expanded numbers of M-CSF-responsive monocyte precursors. On the other hand, SMLR- but not IL3-induced cultures contained expanded numbers of IL3-responsive, immature precursors capable of giving rise to large colonies of monocytic-like cells. Although IL2 could not be detected in SMLR supernatants, both cell growth and IL3 production could be blocked with anti-IL2 receptor and anti-IL2 mAbs. Exogenous IL2, on the other hand, enhanced both cell growth and IL3 production in the SMLR. These results indicate that, under totally autologous conditions, CD4+ autoreactive T-cells do not proliferate in the SMLR, but rather instruct the growth of splenic hematopoietic precursors capable of differentiating along the monocytic lineage. Autoreactive T-cell activation in the SMLR seems to involve minimal IL2 production, which is critically necessary for triggering IL3 production in a markedly amplified manner. These results suggest a link between normal regulation of hematopoiesis and MHC-restricted, autoreactive T-cell activation.

References (23)

  • G. Opeltz et al.

    J. Exp. Med

    (1975)
  • M.E. Weksler et al.

    J. Exp. Med

    (1977)
  • U. Yamashita et al.

    J. Immunol

    (1980)
  • G.A. Dos Reis et al.

    J. Immunol

    (1981)
  • R. Suzuki et al.

    J. Immunol

    (1986)
  • R. Suzuki et al.

    J. Exp. Med

    (1986)
  • T.R. Malek et al.

    J. Immunol

    (1984)
  • K.C. Herold et al.

    Eur. J. Immunol

    (1986)
  • H.M. Johnson et al.

    J. Immunol

    (1985)
  • A.A. Ythier et al.
  • K.C. Gunter et al.

    J. Exp. Med

    (1984)
  • Cited by (13)

    • G-CSF-treated granulocytes inhibit acute graft-versus-host disease

      2006, Blood
      Citation Excerpt :

      One day before transplantation, (C57BL/6 × BALB/c) F1 recipients received 850 cGy total body irradiation (TH780C irradiator with a cobalt Co 60 [60Co] source). For all experiments, 5 × 106 BMTD cells plus 5 × 106 nonadherent nylon wool spleen (NWS)29 cells from C57BL/6 donors were injected intravenously into (C57BL/6 × BALB/c) F1 recipients. NWS cells were from normal donors (NWS) or donors treated for 5 days with rhG-CSF (G-NWS), depleted or not depleted of granulocytes with anti-Gr1 mAb and complement.

    • Normal hematopoiesis is maintained by activated bone marrow CD4<sup>+</sup> T cells

      2005, Blood
      Citation Excerpt :

      In addition, BM engraftment after bone marrow transplantation (BMT) has been shown to depend on T cells, since T-cell–depleted allogeneic BMT (for graft versus host disease [GVHD] prophylaxis) increases the risk of graft failure in about 70% in clinical and experimental approaches.19,20 Complete posttransplantation recovery and HSC maintenance in different animal models suggest a major histocompatibility complex (MHC) class II dependency21,22 and imply a role for CD4+ T cells in hematopoietic recovery. It is yet to be established if the effects of T cells in hematopoiesis are consequent to T-cell activity in the bone marrow or in the periphery.

    • A T cell view of the bone marrow

      2016, Frontiers in Immunology
    View all citing articles on Scopus
    1

    Present address: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.

    View full text