| Recently, attention has been focused on the role of killer cell immunoglobulin-like receptor (KIR)-ligand incompatibility in the graft-versus host direction between donor and recipient in allogeneic hematopoietic stem cell transplantation(ASCT). Killer cell immunoglobulin-like recptors(KIRs) are members of a group of molecules that specifically recognize HLA class I ligands and are found on subsets of human lymphopoetic cells. The number of KIR loci can vary between individuals, resulting in a heterogeneous array of possible KIR genes. The range of observed profiles has been explained by the occurrence of two haplotype families termed A and B which can be distinguished on the basis of certain KIR sequences. Immunogenetic analysis of different ethnic populations shows significant differences in terms of the distribution for group A and group B haplotypes. We studied the frequency of specific KIR genes in Chinese Han population. Here genomic DNA from 79 Chinese Han individuals was typed for the presence or absence of KIR genes. Sixteen KIR genes were observed in the population, and framework genes 3DL3, 3DP1, 2DL4, and 3DL2 were present in all individuals. The most common genotype(observed 40 times) was KIR3DL3-2DL3-2DP1-2DL1-3DP1-2DL4-3DL1-2DS4-3DL2. Twenty-twodifferent genotypes were found. Group A haplotypes outnumbered group B haplotypes in frequency by approximately 3:1, with individuals having two group A haplotypes accounting for 51.9%(41/79). Our data demonstrated that the Chinese Han population is distinct in KIR gene frequencies and putative KIR haplotypes in comparison to some other populations.We also evaluated the role of KIR-ligand mismatch in ASCT patients. Seventy-four allogeneic stem cell transplantation donor/recipient pairs were typed for HLA-A, B, C and KIR. We observed that 57 of 74 (77.3%) donor-recipient pairs could be characterized by lack of recipient HLA ligand for donor KIR. Cumulative incidence analysis of GVHD in all ASCT patients demonstrated a decreased incidence of severe GVHD in patients lacking HLA ligand fordonor-inhibitory KIR (P=0.048), also in AML patients undergoing HLA-identical sibling hematopoietic stem cell transplantation (P=0.03). When compared with patients exhibiting all ligands for known donor-inhibitory KIR, lack of HLA-C group 2 ligand for donor-inhibitory KIR resulted in lower GVHD. Patients lacking 2 ligands (HLA-C and HLA-Bw4) for donor-inhibitory KIR displayed the highest differences in GVHD rates (P=0.03). KIR-mismatch is associated with lower GVHD in Chinese after allogeneic stem cell transplantation. Cumulative incidence analysis of relapse in haploidentical ASCT patients demonstrated a decreased incidence of relapse in patients lacking HLA ligand for donor-inhibitory KIR (P=0.05). When all activating KIRs were analyzed in unrelated HLA identical donor-patient pairs, activating KIRs resulted in higher OS (P=0.002).To explore the rules of the KIR repertoire reconstitution on NK and T cells after allogeneic stem cell transplantation. We sequentially observed healthy donors and transplantation patients before and after HSCT on day +14, +30, +60, +120 and +180, by flow cytometry and determined the expression of CD16, CD56, CD3, CD158a and CD158b. Also we studied the expression pattern of KIR2DL1, KIR2DL2, KIR2DL3, KER3DL1, KIR2DS1, KIR2DS2/4 and KIR2DS3 in peripheral blood of the transplantation patients and healthy people by RT-PCR. Early KIR expression was lower after HSCT . In healthy people, KIR expression on CD16~+CD56~+/CD3~- NK cells was significantly higher than CD16~-CD56~-/CD3~+ T cells. After transplantation, the high frequency of CD158a~+NK was associated with the relapse of leukemia.We constructed the NK-92MI celline without the expression of KIR2DS4. Through flow cytometry, we found that the apoptosis frequency of NK-92MI cell without the expression of KIR2DS4 was lower than normal NK-92MI cell. The NK-92MI cells killing of K562 had no relation with KIR2DS4. |
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