PMID- 14871292 OWN - NLM STAT- MEDLINE DCOM- 20040311 LR - 20190818 IS - 0300-9475 (Print) IS - 0300-9475 (Linking) VI - 59 IP - 2 DP - 2004 Feb TI - Proliferative and cytotoxic response of human natural killer cells exposed to transporter associated with antigen-processing-deficient cells. PG - 159-67 AB - In transporter associated with antigen-processing (TAP)-deficient patients affected by a severe downmodulation of human leucocyte antigen class I (HLA-I) molecules, natural killer (NK) cells have an increased expression of the inhibitory receptor CD94/NKG2A. Focusing our attention on NK cells, we have investigated the phenotype, function and proliferative response of peripheral blood lymphocytes (PBLs) derived from healthy donors after coculturing with TAP (T2)- or HLA-I-deficient (721.221) cell lines and their related HLA-I-expressing transfectants (T3 and DT360, respectively). After 4 days, NK cells cocultured with T2 cells had a threefold increased CD94 expression compared to NK cells cocultured with T3. This increase was due to proliferation of the CD56brightCD94bright subset. In contrast, expression of other inhibitory receptors [killer cell immunoglobulin (Ig)-like receptors] was variable during time and was not related to HLA-I molecules expressed by stimulating cells. Similar results were obtained using HLA-I-deficient cells (721.221). The PBLs cocultured for 4 days with T2 cells displayed enhanced cytotoxic responses. The results suggest that CD56brightCD94bright NK cells are induced to proliferate and kill in response to a TAP-deficient environment. The changes seen in the NK-cell compartment were partially contributed by T lymphocytes present in the coculture. These data could explain the increased CD94 expression and autoimmune manifestations observed in TAP-deficient patients. FAU - Cerboni, C AU - Cerboni C AD - Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden. FAU - Oberg, L AU - Oberg L FAU - Terrazzano, G AU - Terrazzano G FAU - Zappacosta, S AU - Zappacosta S FAU - Carbone, E AU - Carbone E FAU - Karre, K AU - Karre K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Scand J Immunol JT - Scandinavian journal of immunology JID - 0323767 RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Antigens, CD) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (KLRD1 protein, human) RN - 0 (Lectins, C-Type) RN - 0 (NK Cell Lectin-Like Receptor Subfamily D) RN - 0 (transporter associated with antigen processing (TAP)) SB - IM MH - ATP-Binding Cassette Transporters MH - Antigens, CD/immunology MH - Cell Division/immunology MH - Coculture Techniques MH - Cytotoxicity Tests, Immunologic MH - Flow Cytometry MH - Histocompatibility Antigens Class I/*immunology MH - Humans MH - Killer Cells, Natural/cytology/*immunology MH - Lectins, C-Type/immunology MH - Leukocytes, Mononuclear/cytology/immunology MH - NK Cell Lectin-Like Receptor Subfamily D MH - Transfection EDAT- 2004/02/12 05:00 MHDA- 2004/03/12 05:00 CRDT- 2004/02/12 05:00 PHST- 2004/02/12 05:00 [pubmed] PHST- 2004/03/12 05:00 [medline] PHST- 2004/02/12 05:00 [entrez] AID - 1375 [pii] AID - 10.1111/j.0300-9475.2004.01375.x [doi] PST - ppublish SO - Scand J Immunol. 2004 Feb;59(2):159-67. doi: 10.1111/j.0300-9475.2004.01375.x.