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V Colizzi

Publications and source records attributed to V Colizzi.

At least 19 recordsLinked to original sources
PubMed2007

Sphingosine 1-phosphate interferes on the differentiation of human monocytes into competent dendritic cells.

Sphingosine 1-phosphate (S1P) is a lipidic messenger known to exert several physiological functions within the cell. We tested here whether the stimulation of human monocytes with different doses of S1P might interfere with their differentiation into competent dendritic cells (DC). Monocytes cultured with granulocyte macrophage colony stimulating factor, interleukin-4 (IL-4) and S1P differentiated into a DC population lacking CD1a molecules on the surface and acquired some aspects of mature DC (mDC), though in the absence of maturation stimuli. When stimulated with lipopolisaccharide (LPS), CD1a(-) DC produce high amounts of tumour necrosis factor-alpha and IL-10, but not IL-12. Accordingly, these CD1a(-) DC were not capable of stimulating allogenic T lymphocytes so well as CD1a(+) DC generated from untreated monocytes and maturated with LPS. S1P monocyte-derived DC lost their polarizing capacity abrogating the production of gamma-interferon/IL-4 by co-cultured naïve CD4(+)CD45RA(+) T cells. Our findings suggest a mechanism through which S1P can favour the development of immune-related pathological states.

Antigens, CD1↗
PubMed2006

Reduction of mother-to-child transmission of HIV at Saint Camille Medical Centre in Burkina Faso.

One thousand three hundred and twenty-eight pregnant women with less than 32 weeks of amenorrhea received voluntary counseling and testing at Saint Camille Medical Center from May 1, 2002 to December 30, 2004. Following informed consent and pre-test counseling, HIV screening was performed in 1,202 women. According to the prevention protocol, HIV-positive women received a single dose of Nevirapine (200 mg) during their labor, while their newborn received a single dose of Nevirapine (2 mg/kg) within 72 hr from birth. HIV seroprevalence (11.2%) was higher than in the overall population. One hundred and ninety-three children were born at the end of December 2004; 53 children (27.5%) followed a short breastfeeding protocol for 4 months, while 140 (72.5%) were fed artificially. All the children underwent RT-PCR test for HIV 5-6 months after their birth: 173 (89.6%) were HIV negative whilst 20 children (10.4%) were HIV positive. Out of the 20 positive children 5/53 (9.4%) had received breast milk for 4 months, while the remaining 15/140 (10.7%) had been fed artificially (P = 0.814). Artificially fed babies (3/140 (2.1%)) and 1/53 (1.9%) of those breast fed for 4 months deceased according to mortality rate of HIV-positive children. This shows that there is no statistically significant difference (P = 0.648) between the mortality of artificially fed (3/140 or 2.1%) and breast-fed (1/53 or 1.9%) children. Artificially fed children (20/140 (14.3%)) and 5/53 (9.4%) of breast-fed children died within 6-10 months. This figure indicates that there is no significant difference between the mortality rate of artificially and that of breast-fed children (P = 0.427). Although the HIV prevention program reduced significantly the vertical transmission of HIV at Saint Camille Medical Center, the mortality of artificially fed children was still high due to gastrointestinal diseases. The HIV diagnosis by RT-PCR technique was of great help in the early identification of HIV-infected children.

Adolescent↗
PubMed2006

Characterization of drug-resistance mutations in HIV-1 isolates from non-HAART and HAART treated patients in Burkina Faso.

Non-B HIV subtypes have been estimated to account for 88% of HIV infections in the world. These subtypes are particularly relevant in view of the availability of antiretroviral (ARV) drugs, since subtype-specific mutations are associated with drug-resistance in developing countries. Therefore, the pol gene sequences in HIV-1 isolates were examined from the three distinct groups of 39 infected patients from Ouagadougou in Burkina Faso: 17 patients who had not received any antiretroviral therapy (ART); 16 patients received ART, and 6 HIV-infected children, from infected mothers, received a single Nevirapine dose prophylaxis during birth. HIV-1 pol sequencing was successful for 29 samples. As expected, all patients presented the common (non-B subtype) M36I polymorphism and 26/29 (90%) the K20I mutation. Phylogenetic studies showed high predominance of recombinant HIV-1 strains: CRF06_cpx 16/29 (55.17%), CRF02_AG 9/29 (31.03%), A1 2/29 (6.89%), G 1/29 (3.44%), and CRF09_cpx 1/29 (3.44%). Two twins showed, 6 months after birth, a NNRTI-mutation (Y181C/Y). During the same period, the twin mother presented a different NNRTI-mutation (V106I), thus suggesting that the different blood drug concentration may determine a different drug-resistance pathway. Among 17 non-highly active antiretroviral therapy (HAART) patients, 3/17 (17.64%) presented virus with reverse transcriptase (RT) mutations [V118I: 1/17 patients (5.88%), V179E: 2/17 patients (11.76%)]. 10/17 (58.82%) presented virus with minor protease (PR) mutations [L63P: 5/17 patients (29.41%), V77I: 3/17 patients (17.64%), L10I: 2/17 patients (11.76%)]. 4/17 patients did not show any PR and RT mutations (23.52%). Among six HAART-treated patients, 6/6 and 3/6 had M36I and L63LP protease minor subtypes, respectively; and only two (33.33%) presented virus with K103N mutation. The low prevalence of drug-resistant associated mutations in Burkina Faso is encouraging. However, further studies with a larger cohort with a high non-B subtype prevalence are necessary to optimize ART in developing countries.

Adult↗
PubMed2005

Role of mycobacteria-induced monocyte/macrophage apoptosis in the pathogenesis of human tuberculosis.

Apoptosis is a physiological programmed cell death process whose dysregulation plays an important role in different human infectious diseases. An increasing number of intracellular pathogens are known to induce target cell apoptosis, while some other parasites inhibit it. Unlike necrosis, apoptosis is a silent immunological event occurring without inflammation. Infection-induced target cell apoptosis may be a successful strategy to eliminate pathogens and assure host survival. Conversely, apoptosis inhibition could represent an adaptive mechanism for pathogen survival, while it may be beneficial for the host to initiate an effective immune response. The worldwide increase in tuberculosis has stimulated more research aimed at defining the interaction between Mycobacterium tuberculosis and the immune system. M. tuberculosis possesses sophisticated strategies to circumvent its fate within target monocytic cells. Apoptosis of alveolar macrophages and monocytes has been described as a consequence of M. tuberculosis infection. Moreover, the observation that mycobacterial lipoproteins activate macrophages through Toll-like receptor (TLR) 2 suggests that innate immune receptors contribute to defence against M. tuberculosis. There is evidence that TLR-induced apoptosis modulates inflammation and immune activation during M. tuberculosis infection. Finally, the role of apoptotic-infected cells as a source of microbial antigens for cross-priming of effector T-cells is also discussed.

Apoptosis↗
PubMed2004

Expansion of CCR5+ CD4+ T-lymphocytes in the course of active pulmonary tuberculosis.

Nonsyncytium inducing, macrophage tropic HIV strains predominate in the course of active tuberculosis (TB). The present study assesses the expression of CCR5 in CD4+ T-lymphocytes from blood and bronchoalveolar lavage (BAL) of TB patients, non-TB lung disease controls and healthy controls. Memory (CD45RO+), recently activated (CD69+), proliferating (Ki67+) CCR5+ or CCR3+ CD4+ T-lymphocytes were determined by multiparametric flow cytometry analysis. Results show that BAL CD4+ T-lymphocytes expressing CCR5 or CCR3 were significantly increased when compared to peripheral blood both in patients and in healthy controls. However, the data show that the proportions of peripheral blood CCR5+ CD4+ and CCR3+ CD4+ T-lymphocytes and BAL CCR5+ CD4+ T-lymphocytes, but not BAL CCR3+ CD4+ T-lymphocytes, were significantly increased in TB patients. Furthermore, the observation that BAL CCR5+ CD4+ T-lymphocytes from TB patients expressed early activation markers, were not proliferating and showed down-regulation of CCR5 expression suggests recruitment and trapping at the site of disease. Altogether, these results suggest that the lower respiratory tract mucosa may provide cellular targets accessible for efficient transmission of macrophage tropic HIV-1 variants and that tuberculosis may enhance this phenomenon.

Adult↗
PubMed2003

Diagnosis of tuberculosis: available technologies, limitations, and possibilities.

Rapid diagnosis and treatment are important for preventing transmission of Mycobacterium tuberculosis. However, the diagnosis of tuberculosis continues to pose serious problems, mainly because of difficulties in differentiating between patients with active tuberculosis and those with healed lesions, normal mycobacterium boris BCG (Bacillus Calmette Guerin) vaccinated individuals, and unvaccinated Manteux positives. Physicians still rely on conventional methods such as Ziehl-Neelsen (ZN) staining, fluorochrome staining, sputum culture, gastric lavage, and other non-traditional methods. Although the tuberculin test has aided in the diagnosis of tuberculosis for more than 85 years, its interpretation is difficult because sensitization with nontuberculous mycobacteria leads to false-positive tests. There have been numerous unsuccessful attempts to develop clinically useful serodiagnostic kits for tuberculosis. A number of proteinaceous and nonprotein antigens (such as acyltrehaloses and phenolglycolipids) have been explored from time to time for the development of such assays but they have not proved to be clinically useful. It has been difficult to develop an ELISA utilizing a suitable antigen because M. tuberculosis shares a large number of antigenic proteins with other microorganisms that may or may not be pathogenic. With the advent of molecular biology techniques, there have been significant advances in nucleic acid-based amplification and hybridization, which are helping to rectify existing flaws in the diagnosis of tuberculosis. The detection of mycobacterial DNA in clinical samples by polymerase chain reaction (PCR) is a promising approach for the rapid diagnosis of tuberculous infection. However, the PCR results must be corrected for the presence of inhibitors as well as for DNA contamination. In the modern era of genetics, marked by proteomics and genomics, the day is not far off when DNA chip-based hybridization assays will instantly reveal mycobacterial infections.

Antigens, Bacterial↗
PubMed2003

Detailed analysis of the effects of Glu/Lys beta69 human leukocyte antigen-DP polymorphism on peptide-binding specificity.

The polymorphism at position beta69 of the human leukocyte antigen (HLA)-DP molecule has been associated with susceptibility to several immune disorders and alloreactivity. Using molecular modeling, we have predicted a detailed structure of the HLA-DP2 molecule (carrying Glubeta69) complexed with class II associated invariant chain derived peptide (CLIP) and compared it with the form carrying Lys at beta69 (HLA-DP2K69). Major changes between the two models were observed in the shape and charge distribution of pocket 4 and of the nearby pocket 6. Consequently, we analyzed in detail the peptide-binding specificities of both HLA-DP molecules expressed as recombinant proteins. We first determined that the minimum peptide-binding core of CLIP for both HLA-DP2 and DP2K69 is represented by nine aminoacids corresponding to the sequence 91-99 of invariant chain (Ii). We then assessed the peptide-binding specificities of the two pockets and determined the role of position beta69, using competition tests with the Ii-derived peptide CLIP and its mutated forms carrying all the aminoacidic substitutions in P4 and P6. Pocket 4 of HLA-DP2 showed high affinity for positively charged, aromatic, and polar residues, whereas aliphatic residues were disfavored. Pocket 4 of the DP2K69 variant showed a reduced aminoacid selectivity with aromatic residues most preferred. Pocket 6 of HLA-DP2 showed high affinity for aromatic residues, which was increased in DP2K69 and extended to arginine. Finally, we used the experimental data to determine the best molecular-modeling approach for assessing aminoacid selectivity of the two pockets. The results with best predictive value were obtained when single aminoacids were evaluated inside each single pocket, thus, reducing the influence of the overall peptide/ major histocompatibility complex interaction. In conclusion, the HLA-DPbeta69 polymorphism plays a fundamental role in the peptide-binding selectivity of HLA-DP. Furthermore, as this polymorphism is the main change in the pocket 4 area of HLA-DP, it could represent a supertype among HLA-DP molecules significantly contributing to the selection of epitopes presented in the context of this HLA isotype.

Amino Acid Sequence↗
PubMed2003

Role of macrophage phospholipase D in natural and CpG-induced antimycobacterial activity.

The present study addresses the differential ability of macrophages to control intracellular growth of non-pathogenic Mycobacterium smegmatis (Msm) and pathogenic M. tuberculosis (MTB). Results reported herein show that 3 h post infection, intracellular Msm, but not MTB, was significantly killed by macrophages. As the role of human macrophage phospholipase D (PLD) in the activation of antimicrobial mechanisms has been documented, we hypothesised the role of such enzyme in antimycobacterial mechanisms. To this aim, macrophage PLD activity was analysed at different times after exposure with either pathogenic MTB or non-pathogenic Msm. Results showed that, starting from 15 min after mycobacterial exposure, MTB did not induce macrophage PLD activity, whereas the environmental non-pathogenic Msm stably increased it. The direct contribution of PLD in intracellular mycobacterial killing was also analysed by inhibiting enzymatic activity with ethanol or calphostin C. Results show that PLD inhibition significantly increases intracellular Msm replication. In order to see whether the innate PLD-mediated antimicrobial mechanisms against MTB are also induced after CpG ODN stimulation, the role of PLD has been analysed in the course of CpG-mediated intracellular MTB killing. CpG DNA increased PLD activity in both uninfected and MTB-infected macrophages, and the inhibition of PLD activity resulted in a significant reduction of CpG-induced MTB killing. Taken together, our data suggest a relationship between host PLD activation and the macrophage ability to control intracellular mycobacterial growth.

Cell Line↗
PubMed2003

Differential sensitivity of human monocytes and macrophages to ANP: a role of intracellular pH on reactive oxygen species production through the phospholipase involvement.

Atrial natriuretic peptide (ANP), a cardiovascular hormone, elicits different biological actions in the immune system. The aim of the present work was to study the effect of ANP on the intracellular pH (pHi) of human monocytes and macrophages and to investigate whether pHi changes could play a role on phospholipase activities and reactive oxygen species (ROS) production. Human macrophages isolated by peripheral blood mononuclear cells and THP-1 monocytes, which were shown to express all three natriuretic peptide receptors (NPR-A, NPR-B, and NPR-C), were treated with physiological concentrations of ANP. A significant decrease of pHi was observed in ANP-treated macrophages with respect to untreated cells; this effect was paralleled by enhanced phospholipase activity and ROS production. Moreover, all assessed ANP effects seem to be mediated by the NPR-C. In contrast, no significant effect on pHi was observed in THP-1 monocytes treated with ANP. Treatment of macrophages or THP-1 monocytes with 5-(N-ethyl-N-isopropyl)amiloride, a specific Na(+)/H(+) antiport inhibitor, decreases pHi in macrophages and monocytes. Our results indicate that only macrophages respond to ANP in terms of pHi and ROS production, through diacylglycerol and phosphatidic acid involvement, pointing to ANP as a new modulator of ROS production in macrophages.

Amiloride↗
PubMed2002

Proinflammatory cytokines in the course of Mycobacterium tuberculosis-induced apoptosis in monocytes/macrophages.

Mycobacterium tuberculosis (MTB) can induce apoptosis in monocytes/macrophages both in vitro and in vivo, and this phenomenon is associated with mycobacterial survival. The present study addresses the possibility that apoptotic and inflammatory pathways could coexist through a caspase-1-mediated mechanism. In this context, a caspase-1 inhibitor (YVAD), but not caspase-3 (DEVD) or caspase-4 (LEVD) inhibitors, was able to strongly inhibit MTB-induced apoptosis. Moreover, caspase-1 activity was confirmed by the increased maturation of interleukin (IL)-1beta. Of interest, IL-1beta and tumor necrosis factor (TNF)-alpha were produced massively in the course of infection, and both were inhibited by YVAD pretreatment. To determine whether TNF-alpha was produced actively by apoptotic cells, the intracytoplasmatic cytokine content and apoptotic phenotype were analyzed at the single-cell level. Results showed a progressive increase of TNF-alpha production in annexin V-positive cells. These results indicate that MTB-induced apoptosis is associated with proinflammatory cytokine production.

Apoptosis↗
PubMed2002

Inhibition of contact hypersensitivity reaction to picryl chloride: effect of small molecular weight peptidomimetic compounds possessing inhibitory activity against metalloproteinases.

We have studied the effect of small molecular weight inhibitors of snake venom metalloproteinases (SVMP) and matrix metalloproteinases (MMPs) on the induction and effector phase of the contact hypersensitivity reaction (CHR) in a mouse model. Identification of nonsteroid small molecules is very important for the development of new anti-inflammatory drugs. The compounds that we tested were synthetically modified tripeptides (peptidomimetic compounds) POL-257, POL-509, POL-443, POL-491, and POL-647, with structures based on natural occurring peptides in snake venom. A well-known hydroxamate-based inhibitor of the MMPs, Batimastat (BB-94), was also used. We have shown that these peptidomimetics possess in vitro inhibitory activity against the MMP-2 (gelatinase-A), MMP-9 (gelatinase-B), and MMP-3 (stromelysin). They also inhibit metalloproteinases purified from the venom of Crotalus adamanteus and C. atrox snakes, which are very similar to the so-called A Desintegrine, A Metalloproteinase (ADAMs) enzymes. When injected intraperitonealy before the topical application of the contact sensitizer (picryl chloride) or before the challenge, these compounds significantly inhibited the development of CHR. BB-94 at doses 0.4 and 4 mg/kg before the sensitization or before the challenge almost completely abrogated the reaction. POL-257 and POL-443 were among the most active peptidomimetics tested. They inhibited the inflammatory reaction up to 70-80%, when applied either immediately before sensitization or before challenge. POL-509, a methylated derivative of POL-257, inhibited the CHR to 40-50% when administered at either challenge or sensitization. However, when applied 24 h before the challenge, it completely abrogated the inflammatory reaction. The results show that these small molecular weight peptidomimetic compounds, as well as BB-94, are able to significantly inhibit the CHR. This finding opens possibilities for using metalloproteinase inhibitors in the treatment of allergic contact dermatitis and other inflammatory diseases.

Animals↗
PubMed2001

Cross-talk between human monocytes and cancer cells during reactive oxygen intermediates generation: the essential role of hyaluronan.

Human monocytes exhibit considerable cytocidal activity against tumor (but not normal cells) associated, at least partly, with the generation of reactive oxygen intermediates (ROIs). The present study examined the role of surface determinants and hyaluronan (HA) in the induction of ROI production by human monocytes stimulated with cancer cells, as measured by luminol-enhanced chemiluminescence (CL). The inhibitory effect of monoclonal antibodies (MAbs) indicated the engagement of CD18, CD29 and CD44 adhesion molecules. Preincubation of monocytes and tumor cells, expressing CD44 determinants, with either anti-CD44 MAb or HA inhibited CL generation. Addition of HA to monocytes decreased the expression of CD44 and induced CL response. Supernatants from the cultures of tumor cells stimulated CL response of monocytes, an effect that was abolished by treatment of the supernatants with hyaluronidase (HAase) or by preincubation of monocytes with an anti-CD44 MAb. These results indicate that several surface molecules of monocytes, including CD44, are required to trigger the generation of ROI after their contact with tumor cells, whereas HA overexpressed on some cancer cells may allow monocytes (via CD44) to distinguish between transformed and normal cells. However, blocking of CD44 on monocytes by free HA dampens their response to tumor cells. Taken together, these observations suggest that the presence of HA in the tumor stroma may modulate effector functions of infiltrating macrophages and their interactions with cancer cells in situ.

CD18 Antigens↗
PubMed2001

Lipid modification of the Cu,Zn superoxide dismutase from Mycobacterium tuberculosis.

The leader sequence of Mycobacterium tuberculosis Cu,Zn superoxide dismutase (Cu,ZnSOD) contains a prokaryotic membrane lipoprotein attachment site. In the present study, we have found that the protein, which exhibits detectable SOD activity, is lipid-modified and associated with the bacterial membrane when expressed either in M. tuberculosis or in Escherichia coli. These results provide the first demonstration of lipid modification of a Cu,ZnSOD. An analysis of the sodC genes present in available databases indicates that the same signal for lipid modification is also present in the sodC gene products from other mycobacteria and Gram-positive bacteria and, uniquely, in two distinct sodC gene products from the Gram-negative bacterium Salmonella typhimurium. Evidence is also provided for an up-regulation of M. tuberculosis sodC in response to phagocytosis by human macrophages, suggesting that Cu,ZnSOD is involved in the mechanisms that facilitate mycobacterial intracellular growth.

Cell Membrane↗
PubMed2001

Beryllium binding to HLA-DP molecule carrying the marker of susceptibility to berylliosis glutamate beta 69.

Berylliosis is a chronic granulomatous disorder caused by inhalation of Be dusts that is driven by the accumulation of Be-specific CD4+ Th1-cells at disease sites. Susceptibility to berylliosis has been associated with the supratypic variant of HLA-DP gene coding for glutamate at position beta69 (HLA-DPbetaGlu69). The aim of this study was to test the hypothesis that the HLA-DPbetaGlu69 residue plays a role in the interaction with Be. To this end, soluble HLA-DP2 molecule (carrying betaGlu69) and its mutated form carrying lysine at position beta69 (HLA-DP2Lys69) were produced in Drosophila melanogaster and then used in a Be binding assays. BeSO4 (1-1000 microM) was used to compete for the binding of the biotinilated invariant chain-derived peptide CLIP (50 microM). BeSO4 was capable of compete out biotin-CLIP binding from the HLA-DP2 (IC50%: 4.5 microM of BeSO4 at pH 5.0 and 5.5 microM of BeSO4 at pH 7.5), but not from the HLA-DP2Lys69 molecule (IC50%: 480 microM of BeSO4 at pH 5.0 and 220 microM of BeSO4 at pH 7.5). Moreover, the binding of NFLD.M60, a MoAb recognizing an epitope in the HLA-DP peptide binding region, to the HLA-DP2, but not to the HLA-DP2Lys69 soluble molecules was inhibited BeSO4. NFLD.M60 binding to HLA-DP2, but not to HLA-DP2Lys69 stably transfected murine cells was also inhibited by Be both at pH 5.0 and at pH 7.5. The data indicate a direct interaction of Be with the HLA-DPGlu69 molecule, in the absence of antigen processing.

Amino Acid Sequence↗
PubMed2001

Human macrophage gamma interferon decreases gene expression but not replication of Mycobacterium tuberculosis: analysis of the host-pathogen reciprocal influence on transcription in a comparison of strains H37Rv and CMT97.

Mycobacterium tuberculosis is an intracellular pathogen that readily survives and replicates in human macrophages (MPhi). Host cells have developed different mycobactericidal mechanisms, including the production of inflammatory cytokines. The aim of this study was to compare the MPhi response, in terms of cytokine gene expression, to infection with the M. tuberculosis laboratory strain H37Rv and the clinical M. tuberculosis isolate CMT97. Both strains induce the production of interleukin-12 (IL-12) and IL-16 at comparable levels. However, the clinical isolate induces a significantly higher and more prolonged MPhi activation, as shown by reverse transcription-PCR analysis of IL-1beta, IL-6, IL-10, transforming growth factor beta, tumor necrosis factor alpha, and gamma interferon (IFN-gamma) transcripts. Interestingly, when IFN-gamma transcription is high, the number of M. tuberculosis genes expressed decreases and vice versa, whereas no mycobactericidal effect was observed in terms of bacterial growth. Expression of 11 genes was also studied in the two M. tuberculosis strains by infecting resting or activated MPhi and compared to bacterial intracellular survival. In both cases, a peculiar inverse correlation between expression of these genes and multiplication was observed. The number and type of genes expressed by the two strains differed significantly.

Gene Expression Regulation, Bacterial↗
PubMed2001

Macrophage response to Mycobacterium tuberculosis during HIV infection: relationships between macrophage activation and apoptosis.

Human macrophages represent the first line of defense for the containment of Mycobacterium tuberculosis infection. After phagocytosis, macrophages express activation surface markers and produce proinflammatory cytokines and chemokines whose main role is to control pathogen spreading by recruiting peripheral lymphocytes and monocytes at the site of inflammation. However, in the case of a concomitant human immunodeficiency virus (HIV) infection, these signals strongly enhance the susceptibility to viral infection both at the viral entry and replication levels. Under these conditions, viral expansion extends beyond tissue macrophages to T cells and vice-versa, according to the emerging viral phenotype. In absence of an efficient immune response, Mycobacterium tuberculosis can replicate in macrophages in an uncontrolled fashion culminating in macrophage death by apoptosis. As a consequence, a more severe form of immunedepression, involving both innate and specific immune responses, could be responsible for both ematogenous mycobacterial dissemination and extrapulmonary form of tuberculosis in HIV-infected patients.

Apoptosis↗
PubMed2001

Natural T cell immunity to intracellular pathogens and nonpeptidic immunoregulatory drugs.

Natural T (NT) lymphocytes recognize infected cells or microbial compounds without the classical genetic restriction of polymorphic major histocompatibility complex (MHC) molecules. This innate recognition pathway results in a broad and rapid antimicrobial response that may be critical for controlling the spread of intracellular pathogens, requiring the elimination of the infecting agent from both extracellular spaces and host cells. NT cells are mainly composed of alphabeta and gammadelta T lymphocytes that express natural killer (NK) receptors and recognize preferentially various nonpeptidic antigens. Similar to NK cells, NT lymphocytes can 'see' and kill target cells deficient in the expression of one or more MHC class I molecules. NT cells expressing the alphabeta TCR can recognize lipid and lipoglycan antigens presented in the context of nonpolymorphic CD1 molecules, whereas phosphocarbohydrates and akilamines induce constitutive responses in most Vgamma9Vdelta2 NT lymphocytes. The remaining fraction of gammadelta NT cells express the Vdelta1 chain associated with different Vgamma-chains and may directly recognize self-antigens such as MICA, MICB or CD1 molecules. It is possible that NT lymphocytes may play two opposite roles during intracellular infections. First, in the acute phase, they may be critical for the initiation of pathogen elimination. Second, in the chronic phase, NT cells may be dangerous, if their potential autoreactivity is not well controlled. It is conceivable that novel strategies of immune intervention against emerging and re-emerging intracellular pathogens, such as human immundeficiency virus (HIV), hepatitis-C virus (HCV) and Mycobacterium tuberculosis (MTB) may involve the control of NT cell activation/anergy by (nonpeptidic) immunoregulatory drugs.

Acquired Immunodeficiency Syndrome↗