Fixing Indian ink on resection margins.
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Acetic Acid↗
Biomedical subjects
A Salerno
Publications and source records attributed to A Salerno.
Cross-talk between V beta 8+ and gamma delta+ T lymphocytes in contact sensitivity.
We have previously reported that T lymphocytes proliferating in vitro to the hapten trinitrochlorobenzene (TNCB) exhibit a very restricted V beta gene usage and response to TNCB is limited to T-cell receptors (TCR) composed of V beta 8.2 in combination with V alpha 3.2, V alpha 8 and V alpha 10. This paper investigates the role played by T lymphocytes expressing the V beta 8.2 gene segment in the contact sensitivity (CS) reaction to TNCB in the intact mouse and in its passive transfer into naive recipient mice. Mice injected with monoclonal antibodies to V beta 8 are unable to develop CS upon immunization with TNCB and 4-day TNCB-immune lymph node cells from mice that had been depleted in vivo or in vitro of V beta 8+ T lymphocytes fail to transfer CS. However, when separated V beta 8+ and V beta 8- cells were used for passive transfer, it was found that V beta 8+ T lymphocytes failed to transfer CS when given alone to recipient mice and a V beta 8- population was absolutely required. Further analysis revealed that within the V beta 8- population, T lymphocytes expressing the gamma delta TCR were fundamental to allow transfer of the CS reaction. These gamma delta cells were found to be antigen non-specific, genetically unrestricted and to rearrange the V gamma 3 gene segment. This indicates that transfer of the CS reaction requires cross-talk between V beta 8+ and gamma delta+ T lymphocytes, thus confirming our previous results obtained using TNCB-specific T-cell lines. Time-course experiments showed that V beta 8+ lymphocytes taken 4-24 days after immunization with TNCB were able to proliferate and produce interleukin-2 (IL-2) in response to the specific antigen in vitro. Similar time-course experiments were then undertaken using the passive transfer of the CS reaction system. The results obtained confirm that TNCB-specific V beta 8+ T lymphocytes are present in the lymph nodes of immunized mice from day 4 to day 24, and reveal that gamma delta+ T lymphocytes are active for a very short period of time, i.e. days 4 and 5 after immunization. In fact, TNCB-specific V beta 8+ cells are able to transfer CS when taken 4-24 days after immunization, providing the accompanying V beta 8- or gamma delta+ T lymphocyte are obtained 4 days after immunization. In contrast, injection of V beta 8+ T lymphocytes together with V beta 8- or gamma delta+ T lymphocytes that had been taken 2 or 6 days after immunization, failed to transfer significant CS into recipient mice. Taken together, our results confirm that cross-talk between V beta 8+ and gamma delta+ T lymphocytes is necessary for full development of the CS reaction and may explain why the CS reaction in the intact mouse lasts up to 21 days after immunization while the ability of immune lymph node cells to transfer CS is limited to days 4 and 5 after immunization.
Animals↗
Development of hapten-induced IL-4-producing CD4+ T lymphocytes requires early IL-4 production by alphabeta T lymphocytes carrying invariant V(alpha)14 TCR alpha chains.
This paper investigates the mechanisms responsible for the generation of IL-4-producing CD4+ T cells during contact sensitization with the hapten trinitrochlorobenzene (TNCB). Lymph node cells taken 1 day after immunization spontaneously released IL-4 while lymph node cells taken 2 and 3 days after immunization did not produce IL-4. A second wave of IL-4 production that was both antigen-specific and MHC class II (I-A)-restricted was observed 4 days after immunization. The spontaneous release of IL-4 at day 1 was due to the alphabeta+ double-negative (CD4- CD8-) T lymphocytes that also expressed NK1.1 and showed V(alpha)14 rearrangement, while alphabeta+ CD4+ T lymphocytes were the source of the antigen-specific IL-4 production at day 4. Early IL-4 production was required for the development of IL-4-producing CD4+ T cells as mice injected with anti-V(alpha)14 or anti-IL-4 mAb produced little IL-4 and IL-10, while production of IFN-gamma was increased approximately 2-fold. These results indicate that the development of IL-4-producing CD4+ T lymphocytes in the TNCB system requires early production of IL-4 by alphabeta+ double-negative cells carrying invariant V(alpha)14 TCR alpha chain.
Animals↗
Gluten stimulation induces an in vitro expansion of peripheral blood T gamma delta cells from HLA-DQ2-positive subjects of families of patients with celiac disease.
The intestinal gluten sensitivity formally known as celiac disease (CD) is characterized by an evident involvement of local immune response and it is associated with the expression of HLA-DQ2 allele. The major role in the disease seems to be played by the T lymphocyte population bearing gamma delta T cell receptor (T gamma delta cells) which are increased both in peripheral blood and intestinal mucosae of celiac patients. In this paper data on the effects of in vitro gluten stimulation on lymphocytes expressing the T gamma delta phenotype are reported. Gluten seems to be able to induce the expansion of the T gamma delta cell population both in CD patients and their HLA-DQ2-positive asymptomatic relatives, in spite of the absence of clinical evidence of the disease. In addition, the evaluation of gluten-induced cytokine production shows that interleukin-4 could be implied in the early phases of pathogenesis of CD.
Adolescent↗
Early spontaneous improvement and deterioration of ischemic stroke patients. A serial study with transcranial Doppler ultrasonography.
BACKGROUND AND PURPOSE: The purpose of our study was to investigate whether emergency transcranial Doppler (TCD) findings and their modifications over the first 48 hours are related to early neurological changes in acute ischemic stroke patients. METHODS: Ninety-three patients underwent CT scan within 5 hours of a first-ever ischemic hemispheric stroke, and TCD serial examinations at 6, 24, and 48 hours after stroke onset. We classified TCD findings as follows: normal; middle cerebral artery (MCA) asymmetry (asymmetry index between affected and contralateral MCAs below -21%); and MCA no-flow (absence of flow signal from the affected MCA in the presence of ipsilateral anterior and posterior cerebral artery signals through the same acoustic window). We considered early deterioration and early improvement to be a decrease or an increase of 1 or more points, respectively, in the Canadian Neurological Scale score over the same period. RESULTS: At 6-hour TCD examination, MCA asymmetry and MCA no-flow were present in 6 (22%) and 2 (7%), respectively, of 27 improving patients; in 20 (43%) and 10 (22%) of 46 stable patients, and in 9 (45%) and 8 (40%) of 20 deteriorating patients. TCD findings were normal in the remaining patients (P = 0.001). At serial TCD, we detected early (within 24 hours) recanalization (from no-flow to asymmetry or normal and from asymmetry to normal) in 2 (25%) improving patients, in 7 (23%) stable patients, and in 5 (29%) deteriorating patients and late (between 24 and 48 hours) recanalization in 4 (50%) improving patients, in 6 (20%) stable patients, and in none of the deteriorating patients (P = 0.03, chi 2 for trend, improving versus nonimproving irrespective of the timing of recanalization). One deteriorating patient (5%) developed a non-flow from an initial MCA asymmetry. Logistic regression selected normal TCD (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.06 to 0.46) as an independent predictor of early improvement and abnormal TCD (asymmetry plus no-flow) (OR, 5.02; 95% CI, 1.31 to 19.3) as an independent predictor of early deterioration. CONCLUSIONS: TCD examination within 6 hours after stroke can help to predict both early deterioration and early improvement. Serial TCD shows that propagation of arterial occlusion is rarely related to early deterioration, whereas the fact that it can detect early recanalization (within 24 hours) in deteriorating patients and both early and late recanalization (after 24 hours) in improving patients suggests the existence of individual time frames for tissue recovery.
Acute Disease↗
Role of gamma delta T lymphocytes in immune response in humans and mice.
T lymphocytes recognize antigen through the T cell receptor. T cells expressing the gamma delta T cell receptor have been found in many species. Whereas murine alpha beta T cells are concentrated in the lymphoid organs, gamma delta T cells represent only a minor population in the adult thymus and peripheral lymphoid organs (less than 5% of the population). However, murine gamma delta cells predominate in epidermis, in epithelial layers of small intestine, in lung, and in female reproductive organs. In contrast, human gamma delta cells predominate in lymphoid organs. Despite extensive progress in the molecular characterization of the gamma delta T cell receptor and its genes, the physiological role of gamma delta T cells has remained elusive for many years. It is becoming now clear that, in contrast to alpha beta cells that recognize peptide/MHC complexes, gamma delta T cells appear to recognize unprocessed proteic antigens and, in humans, also a class of widely represented nonproteic antigens containing critical phosphate moieties. Similarly, it is now known that gamma delta cells can perform a vast array of immune effector functions and appear to play important roles in antimicrobial immunity as well as in chronic inflammatory reactions.
Animals↗
Development of IFN-gamma-producing CD8+ gamma delta+ T lymphocytes and IL-2-producing CD4+ alpha beta+ T lymphocytes during contact sensitivity.
This paper describes the development of Ag-specific proliferation and the production of IFN-gamma and IL-2 during contact sensitivity (CS) to the hapten picryl chloride (PCl). Lymph node cells from mice immunized with PCl proliferate and produce IFN-gamma and IL-2 when re-exposed to the specific Ag in vitro. Time course experiments showed that the peak IFN-gamma production occurred at days 3 and 4 after immunization, with a sharp decline by day 6. In contrast, proliferation and IL-2 production peaked at day 3 but persisted up to day 10. Proliferation and IFN-gamma and IL-2 production displayed by immune lymph node cells were Ag-specific but required different cell populations. In fact, the production of IFN-gamma was due to a CD8+, gamma delta+ T cell, while proliferation and IL-2 production required the presence of a CD4+, alpha beta+ T cell. Furthermore, IFN-gamma production showed genetic (MHC) restriction, and finer analysis using congenic strains of mice indicated that the K molecule was the restricting element. This was confirmed by blocking the K molecule of the APC used to trigger IFN-gamma production with a specific mAb. In contrast, proliferation and IL-2 production were I-A-restricted, as demonstrated using congenic strains of mice and blocking the I-A molecule of the APCs. Further analysis using purified gamma delta+ cells revealed that these cells produced IFN-gamma in an Ag-specific and MHC (K)-restricted fashion. Injection of mice with a mAb to IL-2 blocked subsequent in vitro proliferation, as well as IL-2 and IFN-gamma production, while all three in vitro responses were unaffected by injection of a mAb to IFN-gamma given at the time of immunization. Furthermore, injection of mice with a mAb to IL-2 blocked the CS reaction when given at the time of immunization, while it had no effect when given at the time of challenge. Injection of mice with mAb to IFN-gamma at the time of challenge reduced but did not abolished CS, suggesting that IFN-gamma is important but not exclusively responsible for the CS reaction.
Animals↗
Three cell subsets are required for the transfer of delayed-type hypersensitivity reaction by antigen-specific T cell lines.
Antigen (trinitrochlorobenzene)-specific T cell lines were obtained by repeated stimulation of lymph node cells from immune mice with antigen in vitro. These T cell lines, consisting of more than 90% CD4+ Vbeta8.2+ and 6 to 9% gammadelta+ T lymphocytes, transfer contact sensitivity (CS) locally when injected at the same site as the challenge antigen, but fail to mediate a systemic passive transfer when injected i.v. Injection of T cell lines together with spleen cells from mice immunized 1 day beforehand (1-day cells) allowed a successful, specific systemic transfer of CS. Phenotypic analysis showed that the 1-day immune cell was alphabeta+, gammadelta-, sIg-, CD3+, CD4-, CD8-, CD5+, B220 (CD45R)+, Thy 1.2+. The effect of 1-day immune cells occurred through a mechanism involving IL-4, as 1-day immune cells failed to allow systemic transfer of CS by T cell lines in recipient mice treated with mAb to IL-4. These observations strongly indicate that three cell subsets are required for the systemic passive transfer of CS by T cell lines: alphabeta+ CD4+, gammadelta+, and a third cell subset, which is CD45R+, alphabeta+, CD3+, but double (CD4, CD8) negative.
Animals↗
gamma delta cells involved in contact sensitivity preferentially rearrange the Vgamma3 region and require interleukin-7.
Ptak and Askenase showed that both alphabeta and gammadelta cells are required for transfer of contact sensitivity (CS). This study confirms that day 4 immune cells depleted of gammadelta cells fail to transfer CS to trinitrochlorobenzene (TNP-Cl) systemically and demonstrates that administration of anti-gammadelta monoclonal antibodies (mAb) in vivo abolishes the CS reaction. Moreover, gammadelta cells accumulate at the antigen challenge site: these cells have the unusual phenotype CD8alpha+, CD8beta-, IL-4 R+ which we suggest is due to their state of activation. Following immunization with contact sensitizer on the skin, the absolute number of gammadelta cells increases in the regional lymph nodes with a peak at 4 days. Of the gammadelta cells, 80 %, both in the lymph nodes of TNP-Cl-immune mice and accumulating at the antigen challenge site are Vgamma3+. The gammadelta cells expressing Vgamma3, which is characteristic of dendritic epithelial T cells (DETC), obtained 4 days after sensitization, proliferate in response to interleukin (IL)-7, but only poorly to IL-2 and IL-4. They also respond to concanavalin A and immobilized anti-gammadelta mAb, but not to haptens or heat-shocked syngeneic spleen cells. Furthermore, injection of mice with mAb to IL-7 inhibits accumulation of Vgamma3+ cells both in the lymph nodes after skin sensitization and at the antigen-challenge site. Altogether, these results strongly support the view that DETC are related to, or the original source of, the gammadelta cells found in the lymph node after skin sensitization and at the site of challenge, and that IL-7 is implicated in these phenomena.
Animals↗
Somatosensory evoked potentials elicited by stimulation of lower-limb nerves in amyotrophic lateral sclerosis.
To determine lower limb somatosensory modifications in amyotrophic lateral sclerosis (ALS), we studied somatosensory evoked potentials (SEPs) elicited by stimulation of tibial posterior nerves (TP), sural nerves (SN), saphenous internous nerves (SA), and medial plantar nerves (PL) of both limbs in 24 ALS patients, and compared the results with those from 17 normal subjects. Responses were recorded according to the international 10-20 system. Normal sensory conduction velocities of SN, SA and PL and H reflexes in soleus muscles were prerequisites for patient inclusion in this study. The results showed marked alterations in SEPs cortical components of all lower limb nerves, which could be related to abnormal sensory transmission (after spinal N22), or cortical abnormalities. We put forward the hypothesis of impairment of pyramidal control of the sensory system and Clark's column involvement to explain such anomalies. It was concluded that SEPs abnormalities in the lower limbs are a common feature in ALS.
Aged↗
Patterns of phosphoantigen stimulation of human Vgamma9/Vdelta2 T cell clones include Th0 cytokines.
This paper examines functional properties of human Vgamma9/Vdelta2 T cell lines and clones generated by in vitro culture with synthetic and natural (mycobacterial) phosphoantigenic molecules. It confirms the broad reactivity of Vgamma9/Vdelta2 T cell lines and clones toward phosphoantigens. Optimal recognition of phosphoantigens by Vgamma9/Vdelta2 T cells required accessory cells to occur, but did not require specialized antigen presenting cells. However, species origin of the APC was irrelevant as proliferation of Vgamma9/Vdelta2 T cells occurred in the presence of syngeneic, allogeneic or xenogeneic APC and was not restricted to APC of particular tissue origin. Moreover antigen uptake and processing was not required for recognition by Vgamma9/ Vdelta2 cells, as evidenced by the ability of fixed APCs to present phosphoantigens. Similarly, the expression of classical MHC class I and class II molecules was not required for phosphoantigen recognition by gammadelta T cells. However, gammadelta T cell clones responded to stimulation by several cytokines including IL-12, IFNgamma and TNFalpha. Finally, Vgamma9/Vdelta2 T cell clones preferentially produced both IFN-gamma and IL-4 in response to PHA or TUBAg stimulation, revealing that a Th0 pattern of cytokine production is frequent among these cells.
Antibodies, Bacterial↗
TCR V alpha chain expression influences reactivity to the hapten TNP.
We have recently demonstrated a remarkable selection of in vitro cultivated, TNP-specific polyclonal T cell lines for the expression of a TCR beta chain encoded by the V beta 8.2 gene. The goal of the present study was to analyse V alpha usage in V beta 8.2 T cells responsive to TNP, using TNP-specific T cell lines derived from three common strains of mice, as well as from V beta 8.2 transgenic mice. Results indicate that in vitro TNP stimulation of T cells from TNP-immune mice results in significant skewing of V alpha usage among responding V beta 8.2+ T cells, with overexpression observed for V alpha 3.2 and V alpha 8. These results indicate that V alpha expression influences recognition of TNP by T cells, and suggest that the hapten TNP might be recognized like typical peptide antigens by combinatorial TCR alpha and beta contact sites.
Animals↗
[Phase-sensitive modulation thermography as a new method for non-contact in vitro measurement of the human tooth].
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Computer Graphics↗
Interleukin 4 suppresses primary interferon gamma response by T cells immunized in vivo and cultured in vitro with interleukin 2.
This paper describes a novel primary in vivo/in vitro culture system which allows analysis of the effect of IL-4 added to culture 1 day after immunization on the production of IFN-gamma. Mice are immunized epicutaneously with picryl chloride (TNP) and draining lymph node cells were harvested 1 day later. These cells (1 day lymph node cells), when cultured in vitro for 3 days in the presence of IL-2, either continuously or as a pulse, give an IFN-gamma response on reexposure to antigen 3 days later. This production of IFN-gamma is both antigen-specific and genetically (MHC)-restricted and is due to both CD8+ and CD4+ T cells. However, if 1 day lymph node cells are cultured with both IL-2 and IL-4, no IFN-gamma is produced on subsequent reexposure to antigen, but the cells acquire the ability to produce IL-4 and IL-10. Moreover, cells pulsed with IL-4 blocked IFN-gamma production when cocultured with cells pulsed with IL-2. IL-4 only exerted its inhibitory activity on IFN-gamma production when added on the first or second day of culture and had no effect at later times. Finally, the inhibitory activity of IL-4 on IFN-gamma production may depend on the production of IL-10, induced by the IL-4, as the inhibitory effect of IL-4 is reversed by mAb against IL-10.
Animals↗
Cytokine production pathway in the elderly.
It is well known that aging is associated with various alterations in lymphoid cell functions, particularly with a progressive decline in immune responsiveness to exogenous antigens and increasing incidence of autoimmune phenomena. Many studies have been focused on the mechanisms of the immunologic features of aging. this review describes our results of studies performed to determine the influence of age on the capacity to produce interleukin-2 (IL-2), interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-t (IL-5), interleukin-6 (IL-6) and tumor necrosis factor (TNF). Mitogen-stimulated cultures of mononuclear cells (MNC) from human beings were assessed for cytokine-producing capacity. A significant decrease in IFN-gamma and IL-2 production by MNC cultures from elderly individuals was observed. No significant difference was instead observed between cultures from elderly individuals and those from young ones as regards TNF-alpha, IL-4 and IL-6 production. Mitogen or antigen-stimulated cultures of MNC from aged mice also displayed a significant decrease in IFN-gamma and IL-2 production as well as TNF-beta. Instead IL-4 and IL-5 production significantly increased in these cultures. We suggest that this imbalanced cytokine production may well account for the pattern of immune response which may be observed in the elderly, i.e. a normal or increased humoral response (including autoimmune responses) in face of a low T cell immune responsiveness.
Aged↗
[Alterations of various parameters of evoked motor potentials in amyotrophic lateral sclerosis].
To assess their interest, we studied different motor evoked potentials (MEP) parameters in 18 amyotrophic lateral sclerosis (ALS) patients and compared them to those obtained in 20 subjects unaffected by neurological diseases: cortical threshold (CT), latency and amplitude of primary responses (PR), central conduction time (CCT), silent period (SP) contralateral to the stimulated cortex and late muscular responses (LMR). In normal subjects MEP parameters were in agreement with those described in the literature, except for LMR. These were only recorded in upper limbs with latencies around 200 ms in 9 out of 20 subjects. In ALS patients, LMR were not modified as compared to normal subjects. Except for mean CCT, in upper and lower limbs, all parameters were altered. We conclude that all MEP parameters are useful in ALS and disclose the involvement of the entire pyramidal tract in this disease.
Amyotrophic Lateral Sclerosis↗
Role of IL-4 in delayed type hypersensitivity.
IL-4 plays a key role in the contact sensitivity skin reaction. This has several implications. First, the view that contact sensitivity (CS) is only mediated by cells with a Th1 profile of cytokine secretion needs modification, in the light of the essential role of IL-4 at the effector stage. Second, the concept of a single cell involved in the systemic transfer of CS is no longer tenable, as it is known that both alpha beta and gamma delta cells are required. Studies with the cell lines (which contain both alpha beta and a few gamma delta cells) suggest that this double requirement may involve the action of IL-4 on gamma delta cells, which bear receptors for IL-4. Finally, the view that T cell lines only transfer CS when injected locally, but not when injected intravenously (systemic transfer), is correct but incomplete, as T cell lines actually give systemic transfer of CS, providing the cell line or the recipient is treated with IL-4.
Animals↗
Major histocompatibility complex regulation of cytokine production.
This review describes the phenomenon of the major histocompatibility complex (MHC) control of cytokine production both in experimental animals and in humans. H-2 (mouse MHC) regulates which type of cytokine is selectively produced in response to the hapten trinitrophenyl (TNP). T cells from TNP-immune H-2k mice produce interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-3, IL-5, tumor necrosis factor-alpha (TNF-alpha), IL-10, and very low levels of IL-4 on reexposure to the specific antigen in vitro. By contrast, T cells from H-2d mice produce IL-3, TNF-alpha, IL-10, and IL-4 but very low levels of IL-2, IL-5 and IFN-gamma. As MHC-congenic matched strains (BALB/k and BALB/c) are used, this makes it unlikely that non-MHC genes influence the class of response observed. A similar pattern of haplotype regulation of cytokine production is observed in humans. In fact, peripheral blood mononuclear cells from HLA-B8,DR3-positive and negative individuals differ in their ability to produce IL-2, IL-5, and IFN-gamma on stimulation with the mitogen phytohemagglutinin while producing similar amounts of IL-4, IL-6, and IL-10. The following main considerations emerge from these observations. The MHC/peptide complex generated after antigen immunization, indicates which class of cytokine production is preferentially induced and, therefore, the outcome of the immune response. Furthermore, MHC genotype may affect cytokine production (and then immune responses) by completely different mechanism(s), that is, by an antigen-nonspecific control that does not depend on the ability of MHC molecules to bind in different ways the different peptides. Accurate control of the functional repertoire of an immune response is a critical parameter in response to infections as well as in immunopathology. MHC control of the class of the immune response at the level of cytokine production is a sophisticated way in which this occurs. This control might be involved in adaptive immune responses to infections as well as in immunopathology.
Animals↗