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Sca1(+)/Mac1(+) nitric oxide-producing cells in the spleens of recipients early following bone marrow transplant suppress T cell responses in vitro. Cell Immunol 1998 Nov 01;189(2):149-59

Date

10/29/1998

Pubmed ID

9790729

DOI

10.1006/cimm.1998.1373

Scopus ID

2-s2.0-0032211707   11 Citations

Abstract

Spleen cells collected from allogeneic chimeras early after bone marrow transplantation (BMT) consistently showed suppressed proliferative responses to interleukin-2 in vitro and failed to proliferate in mixed lymphocyte reaction (MLR) assays. However, isolation of Thy 1.2(+) T cells from the heterogeneous spleen cell suspension prior to culture resulted in heightened proliferation, suggesting the presence of cells capable of suppressing T cell responses in vitro. When separated into subpopulations by negative and positive selection with specific monoclonal antibodies, a non-T, non-B population with immunosuppressive properties was identified. The suppressive cells were found in the spleens of both allogeneic and syngeneic chimeras, but not normal donor mice. Suppressor activity was transient and typically declined by 3 weeks post-BMT. The cells suppressed the response of alloactivated T cells isolated from BMT chimeras as well as naive donor T cells in MLR assays in a dose-dependent manner. To explore the mechanism(s) involved in the suppression, the effects of interferon-gamma (IFN-gamma)-specific mAb and the nitric oxide (NO) synthase inhibitor NG-methyl-l-arginine were examined. The results support a role for both IFN-gamma and NO in the suppressive activity. Separation of cells based on Mac-1 expression indicated that there were both Mac-1-enriched and Mac-1-depleted cells capable of producing NO, but that the Mac-1-depleted cells were the most potent suppressors in MLR assays. The Mac-1-depleted cells still contained a residual population of Mac-1(dim) cells which showed increased levels of Mac-1 expression after overnight culture. Intracellular staining with an inducible nitric oxide synthase (iNOS)-specific mAb indicated that the NO-producing cells expressed the cell surface markers Mac-1 and Sca-1. When iNOS knockout transgenic mice were used as transplant donors, in vitro suppression of T cell responses was reduced but not eliminated, suggesting that other mechanism(s) could contribute to the suppression. Collectively, these results demonstrate that Sca-1(+)/Mac-1(+) cells capable of producing NO are present in the spleens of recipients early after BMT and suggest that these cells may have immunoregulatory roles in vivo.

Author List

Johnson BD, Hanke CA, Becker EE, Truitt RL

Author

Bryon D. Johnson PhD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Bone Marrow Transplantation
Interferon-gamma
Lipopolysaccharides
Lymphocyte Activation
Macrophage-1 Antigen
Mice
Mice, Inbred AKR
Mice, Inbred BALB C
Mice, Knockout
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Spleen
T-Lymphocytes, Regulatory
Transplantation, Homologous
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc