Please review the following:

Persistence of pathological distribution of NK cells in HIV-infected patients with prolonged use of HAART and a sustained immune response. PLoS One. 2015 Mar 26;10(3):e0121019.

 Frias M(1), Rivero-Juarez A(1), Gordon A(1), Camacho A(1), Cantisan S(1),

Cuenca-Lopez F(1), Torre-Cisneros J(1), Peña J(2), Rivero A(1).

OBJECTIVE: A prospective analysis of the distribution of NK subsets and natural cytotoxicity receptors (NKp30/NKp46) in HIV patients with long-term HAART use and sustained virological and immunological response.

METHODS: The main inclusion criteria were: at least 3 years' receipt of HAART; current CD4+ count ≥ 500 cells/mm3; undetectable viral load for at least 24 months; no hepatotropic virus co-infection. Percentages of CD56dim, CD56bright NK cells and CD56neg CD16+ cells were obtained. Expression of the NCRs, NKp30 and NKp46 was analysed in CD56+ cells. Thirty-nine infected patients and sixteen healthy donors were included in the study.

RESULTS: The percentages of total CD56+ and CD56dim NK cells were significantly lower in HIV-infected patients than in healthy donors (70.4 vs. 50.3 and 80.9 vs. 66.1 respectively). The percentage of total CD56+ NK cells expressing NCR receptors was lower in HIV patients than in healthy donors (NKp30: 25.20 vs. 58.63; NKp46: 24.8 vs. 50.59). This was also observed for CD56dim and CD56bright NK cells. Length of time with undetectable HIV viral load was identified as an independent factor associated with higher expression of NKp30 and NKp46. 

CONCLUSION: Despite the prolonged and effective use of HAART, HIV-infected patients do not fully reconstitute the distribution of NK cells. Length of time with an undetectable viral load was related to greater recovery of Kp30/NKp46 receptors.

Human NK cell response to pathogens. Semin Immunol. 2014 Apr;26(2):152-60.

 Della Chiesa M(1), Marcenaro E(1), Sivori S(1), Carlomagno S(1), Pesce S(1),

Moretta A(2).

 NK cells represent important effectors of the innate immunity in the protection

of an individual from microbes. During an NK-mediated anti-microbial response,

the final fate (survival or death) of a potential infected target cell depends

primarily on the type and the number of receptor/ligand interactions occurring at

the effector/target immune synapse. The identification of an array of receptors

involved in NK cell triggering has been crucial for a better understanding of the

NK cell biology. In this context, NCR play a predominant role in NK cell

activation during the process of natural cytotoxicity. Regarding the NK-mediated

pathogen recognition and NK cell activation, an emerging concept is represented

by the involvement of TLRs and activating KIRs. NK cells express certain TLRs in

common with other innate cell types. This would mean that specific TLR ligands

are able to promote the simultaneous and synergistic stimulation of these innate

cells, providing a coordinated mechanism for regulating the initiation and

amplification of immune responses. Evidences have been accumulated indicating

that viral infections may have a significant impact on NK cell maturation,

promoting the expansion of phenotypically and functionally aberrant NK cell

subpopulations. For example, during chronic HIV-infection, an abnormal expansion

of a dysfunctional CD56neg NK cell subset has been detected that may explain, at

least in part, the defective NK cell-mediated antiviral activity. An analogous

imbalance of NK cell subsets has been detected in patients receiving HSCT to cure

high risk leukemias and experiencing HCMV infection/reactivation. Remarkably, NK

cells developing after CMV reactivation may contain "memory-like" or "long-lived"

NK cells that could exert a potent anti-leukemia effect.

Healthy Neonates Possess a CD56-Negative NK Cell Population with Reduced

Anti-Viral Activity. PLoS One. 2013 Jun 21;8(6):e67700.

 Jacobson A(1), Bell F, Lejarcegui N, Mitchell C, Frenkel L, Horton H.

 BACKGROUND: Neonatal Natural Killer (NK) cells show functional impairment and expansion of a CD56 negative population of uncertain significance.

METHODS: NK cells were isolated from cord blood and from adult donors. NK subpopulations were identified as positive or negative for the expression of CD56 and characterized for expression of granzyme B and surface markers by multi-parameter flow cytometry. Cell function was assessed by viral suppression and cytokine production using autologous lymphocytes infected with HIV. Activating (NKp30, NKp46) and inhibitory (Siglec-7) markers in healthy infants and adults were compared with viremic HIV-infected adults.

RESULTS: Cord blood contained increased frequencies of CD56 negative (CD56neg) NK cells with reduced expression of granzyme B and reduced production of IFNγ and the CC-class chemokines RANTES, MIP1α and MIP1β upon stimulation. Both CD56pos and CD56neg NK subpopulations showed impaired viral suppression in cord blood, with impairment most marked in the CD56neg subset. CD56neg NK cells from cord blood and HIV-infected adults shared decreased inhibitory and activating receptor expression when compared with CD56pos cells.

CONCLUSIONS: CD56neg NK cells are increased in number in normal infants and these effectors show reduced anti-viral activity. Like the expanded CD56neg population described in HIV-infected adults, these NK cells demonstrate functional impairments which may reflect inadequate development or activation.