Abstract
Natural killer cells mediate the specific rejection of bone marrow cell (BMC) allografts in lethally irradiated mice. The Ly-49 family of molecules present on subsets of murine NK cells appears capable of binding class I MHC molecules, resulting in transmission of an inhibitory signal to the NK cell. These Ly-49 family members have been shown to have an immunoreceptor tyrosine-based inhibitory motif that is responsible for the inhibitory signal. However, a new Ly-49 family member was found that lacks this motif, Ly-49D, and evidence suggests that this may be an activating receptor. We therefore compared the role of the activating Ly-49 member with NK cells bearing inhibitory Ly-49 receptors in BMC rejection. Depletion of Ly-49D+ NK cells in H-2b mice abrogated their ability to reject H-2(d) BMC allografts. Similarly, Ly-49C+ NK cells also were shown to mediate the specific rejection of H-2(d) BMC. When both subsets were depleted, an additive enhancement of BMC engraftment was observed, indicating that both subsets play a role in the rejection of allogeneic H-2-homozygous H-2(d) BMC. However, rejection of H-2(b x d) or D8 (H-2b, D(d) transgene) BMC allografts was unaffected by Ly-49C+ NK cell depletion in H-2b mice. In marked contrast, depletion of Ly-49D+ NK cells in H-2b mice totally abrogated the rejection of H-2(b x d) heterozygous BMC in support of in vitro data suggesting that Ly-49D+ NK cells receive activating signals. Therefore, NK subsets demonstrate a differential ability to reject H-2 homozygous and heterozygous BMC.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 87-94 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 160 |
| Issue number | 1 |
| State | Published - Jan 1 1998 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
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Differential effects of the rejection of bone marrow allografts by the depletion of activating versus inhibiting Ly-49 natural killer cell subsets. / Raziuddin, Arati; Longo, Dan L.; Mason, Llewellyn; Ortaldo, John R.; Bennett, Michael; Murphy, William J.
In: Journal of Immunology, Vol. 160, No. 1, 01.01.1998, p. 87-94.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential effects of the rejection of bone marrow allografts by the depletion of activating versus inhibiting Ly-49 natural killer cell subsets
AU - Raziuddin, Arati
AU - Longo, Dan L.
AU - Mason, Llewellyn
AU - Ortaldo, John R.
AU - Bennett, Michael
AU - Murphy, William J
PY - 1998/1/1
Y1 - 1998/1/1
N2 - Natural killer cells mediate the specific rejection of bone marrow cell (BMC) allografts in lethally irradiated mice. The Ly-49 family of molecules present on subsets of murine NK cells appears capable of binding class I MHC molecules, resulting in transmission of an inhibitory signal to the NK cell. These Ly-49 family members have been shown to have an immunoreceptor tyrosine-based inhibitory motif that is responsible for the inhibitory signal. However, a new Ly-49 family member was found that lacks this motif, Ly-49D, and evidence suggests that this may be an activating receptor. We therefore compared the role of the activating Ly-49 member with NK cells bearing inhibitory Ly-49 receptors in BMC rejection. Depletion of Ly-49D+ NK cells in H-2b mice abrogated their ability to reject H-2(d) BMC allografts. Similarly, Ly-49C+ NK cells also were shown to mediate the specific rejection of H-2(d) BMC. When both subsets were depleted, an additive enhancement of BMC engraftment was observed, indicating that both subsets play a role in the rejection of allogeneic H-2-homozygous H-2(d) BMC. However, rejection of H-2(b x d) or D8 (H-2b, D(d) transgene) BMC allografts was unaffected by Ly-49C+ NK cell depletion in H-2b mice. In marked contrast, depletion of Ly-49D+ NK cells in H-2b mice totally abrogated the rejection of H-2(b x d) heterozygous BMC in support of in vitro data suggesting that Ly-49D+ NK cells receive activating signals. Therefore, NK subsets demonstrate a differential ability to reject H-2 homozygous and heterozygous BMC.
AB - Natural killer cells mediate the specific rejection of bone marrow cell (BMC) allografts in lethally irradiated mice. The Ly-49 family of molecules present on subsets of murine NK cells appears capable of binding class I MHC molecules, resulting in transmission of an inhibitory signal to the NK cell. These Ly-49 family members have been shown to have an immunoreceptor tyrosine-based inhibitory motif that is responsible for the inhibitory signal. However, a new Ly-49 family member was found that lacks this motif, Ly-49D, and evidence suggests that this may be an activating receptor. We therefore compared the role of the activating Ly-49 member with NK cells bearing inhibitory Ly-49 receptors in BMC rejection. Depletion of Ly-49D+ NK cells in H-2b mice abrogated their ability to reject H-2(d) BMC allografts. Similarly, Ly-49C+ NK cells also were shown to mediate the specific rejection of H-2(d) BMC. When both subsets were depleted, an additive enhancement of BMC engraftment was observed, indicating that both subsets play a role in the rejection of allogeneic H-2-homozygous H-2(d) BMC. However, rejection of H-2(b x d) or D8 (H-2b, D(d) transgene) BMC allografts was unaffected by Ly-49C+ NK cell depletion in H-2b mice. In marked contrast, depletion of Ly-49D+ NK cells in H-2b mice totally abrogated the rejection of H-2(b x d) heterozygous BMC in support of in vitro data suggesting that Ly-49D+ NK cells receive activating signals. Therefore, NK subsets demonstrate a differential ability to reject H-2 homozygous and heterozygous BMC.
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UR - http://www.scopus.com/inward/citedby.url?scp=0031883535&partnerID=8YFLogxK
M3 - Article
C2 - 9551959
AN - SCOPUS:0031883535
VL - 160
SP - 87
EP - 94
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -