SummaryNatural kiUer (NK) cell dones have been previously described which are inhibited by HLA-C aUdes with Asn77-LysS0 (NKl-specific cdls) or by HLA-C alldes with Ser77-Asn80 (NK2-specific ceils). In the present work, the generation of NK cells with HLA-B-rdated spedficities was attempted by stimulation of a Bw4 homozygous responder by a Bw6 homozygous donor. Two NK clones were found, which were inhibited by HLA-Bw4 (but not by HLA-Bw6) allotypes and by some HLA-A allotypes that share the Bw4 public epitope. Inhibition of NK cell-mediated lysis strongly correlated with the presence of an Ile residue at position 80 of the protective allele. These NK cdl dones define a new specificity termed NK3.

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Pericytes are branched cells located in the wall of capillary blood vessels that are found throughout the body, embedded within the microvascular basement membrane and wrapping endothelial cells, with which they establish a strong physical contact. Pericytes regulate angiogenesis, vessel stabilization, and contribute to the formation of both the blood-brain and blood-retina barriers by Angiopoietin-1/Tie-2, platelet derived growth factor (PDGF) and transforming growth factor (TGF) signaling pathways, regulating pericyte-endothelial cell communication. Human pericytes that have been cultured for a long period give rise to multilineage progenitor cells and exhibit mesenchymal stem cell (MSC) features. We focused our attention on the roles of pericytes in brain and ocular diseases. In particular, pericyte involvement in brain ischemia, brain tumors, diabetic retinopathy, and uveal melanoma is described. Several molecules, such as adenosine and nitric oxide, are responsible for pericyte shrinkage during ischemia-reperfusion. Anti-inflammatory molecules, such as IL-10, TGFβ, and MHC-II, which are increased in glioblastoma-activated pericytes, are responsible for tumor growth. As regards the eye, pericytes play a role not only in ocular vessel stabilization, but also as a stem cell niche that contributes to regenerative processes in diabetic retinopathy. Moreover, pericytes participate in melanoma cell extravasation and the genetic ablation of the PDGF receptor reduces the number of pericytes and aberrant tumor microvessel formation with important implications for therapy efficacy. Thanks to their MSC features, pericytes could be considered excellent candidates to promote nervous tissue repair and for regenerative medicine.

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We analyzed the recently defined ability of CD3-CD16+ cells to specifically recognize and lyse normal allogeneic target cells (PHA-induced blasts). The susceptibility to lysis by a given alloreactive natural killer (NK) clone ("1 anti-A") was expressed by PHA blasts derived from 9 of 38 random donors analyzed. In all instances, the specific lysis of "susceptible" target cells was greater than 35% while that of "nonsusceptible" targets was less than 6% at an E/T cell ratio of 5:1. In addition to 1 anti-A, A anti-1 specific CD3-CD16+ clones could also be isolated from the reverse MLC combination. The relationship existing between lysis of normal allogeneic cells or tumor cells by the same CD3-CD16+ effector cell has been investigated: 1 anti-A specific CD3-CD16+ clones lysed PHA blasts of three of six cancer patients, while they lysed fresh tumor cells (ovarian carcinoma) from all six patients. The type of inheritance of the character "susceptibility to lysis" was analyzed in representative families. This analysis revealed that the character is inherited in an autosomic recessive fashion, and it is therefore different from MHC. We further investigated the type of segregation of the opposite character "resistance to lysis" (which is inherited in a dominant mode). The finding that this character segregated in all donors expressing given MHC haplotypes indicated that the gene regulating the expression of the NK-defined alloantigen is present on chromosome 6.