Supplementary Materials Supplemental material supp_89_19_9909__index. all possible combinations of CD107a manifestation and gamma interferon (IFN-) and CCL4 secretion. The highest frequency of practical NK cells responding to HLA-null cell activation was the NKG2A+ 3DL1+ NK cell populace. The highest frequencies of practical NK cells responding to autologous iCD4 cells were those expressing NKG2A; coexpression of 3DL1 did not further modulate responsiveness. This was the case for the practical subsets characterized by the sum of all functions tested (total responsiveness), as well as from the trifunctional CD107a+ IFN-+ CCL4+, CD107a+ IFN-+, total CD107a+, Porcn-IN-1 and total IFN-+ practical subsets. These results indicate the NKG2A receptor has a part in NK cell-mediated anti-HIV reactions. IMPORTANCE HIV-infected CD4 (iCD4) cells activate NK cells, which then control HIV replication. However, little is known concerning which NK cell populations iCD4 cells stimulate to develop antiviral activity. Here, we examine the rate of recurrence of NK cell populations, defined from the presence/absence of the NK cell receptors (NKRs) NKG2A and 3DL1, that respond to iCD4 cells. NKG2A and 3DL1 are involved in priming NK cells for antiviral functions upon encountering virus-infected cells. A higher rate of recurrence of NKG2A+ than NKG2A? NK cells responded to iCD4 cells by developing antiviral functions such as CD107a manifestation, which correlates with NK cell killing, and secretion of gamma interferon and CCL4. Coexpression of 3DL1 within the NKG2A+ and NKG2A? NK cells did not modulate reactions to iCD4 cells. Understanding the mechanisms underlying the connection of NK cells with iCD4 cells that lead to HIV control may contribute to developing strategies that harness NK cells for avoiding or controlling HIV infection. Intro Natural killer (NK) cells are a subset of lymphocytes that mediate immune reactions against virally infected and transformed cells (1). They contribute to innate immune defenses directly by eliciting functions such as cytotoxicity and the secretion of cytokines and chemokines. They also contribute to shaping adaptive immune reactions through their relationships with dendritic cells (2). NK cell activation can occur without prior sensitization before T cell-mediated immune responses can be induced (3). The timing of NK cell reactions suggests that they may possess a role in initial viral control. This is supported by studies that implicate NK cells in resistance to human being immunodeficiency computer virus (HIV) (4,C6). NK cells also appear to play a role in several viral infections (HIV, human being cytomegalovirus [HCMV], hepatitis B computer virus [HBV], hepatitis C computer virus [HCV], and influenza computer virus) (7,C11). The importance of NK cell function in the context of HIV illness is highlighted from the development of HIV sequence polymorphisms that allow the Goat polyclonal to IgG (H+L)(HRPO) computer virus to evade NK cell antiviral pressure (12). The state of activation of NK cells is determined by the integration of signals received from stochastically indicated germ line-encoded cell surface receptors upon connection with ligands on target cells. NK cells acquire practical competence through an ontogenic process known as education, which requires the connection of inhibitory NK receptors (iNKRs) Porcn-IN-1 with their cognate HLA ligands on neighboring cells (13, 14). Education is not an on/off switch as features can be tuned by the number of iNKRs engaged, the Porcn-IN-1 strength of relationships between NKRs and their ligands, and the absence or presence of activating NK cell receptor (aNKR) engagement (15, 16). NK cells lacking iNKRs for self-HLA ligands remain uneducated and hyporesponsive (14). Educated NK cells are tolerant of normal healthy cells but have the potential to respond to target cells that upregulate ligands for aNKRs and have reduced levels of cell surface HLA ligands for iNKRs, as often.