Biomedical subjects

F Dieli

Publications and source records attributed to F Dieli.

At least 19 recordsLinked to original sources

PubMed2000

Evidence of alloreactive T lymphocytes in fetal liver: implications for fetal hematopoietic stem cell transplantation.

The use of hematopoietic stem cells for in utero transplantation to create permanent hematochimerism represents a new concept in fetal therapy, although this approach has provided heterogeneous results. In this paper we have undertaken molecular, phenotypic and functional studies aimed at identifying the presence of fully competent T lymphocytes in samples of fetal livers and cord blood. We found mature VDJ TCR beta chain transcripts in fetal liver cells taken from 7 to 16 weeks of gestation and a similar pattern was detected in cord blood cells sampled from 13.5 to 20.5 weeks of gestation. A Vbeta8 gene sequence comparable to that detected in adult PBMC was found in fetal liver samples at 9 or 17 weeks gestation. PreTalpha message was detected in all samples and its expression decreased in fetal blood samples with increasing gestational age while Calpha message appeared at 9.4 weeks and its expression increased during gestational age. T cell clones obtained from fetal liver cells showed a mature TCR alphabeta+, CD8+ phenotype and displayed strong alloreactivity against allo-MHC class I molecules. The presence of alloreactive T lymphocytes may explain the failure to engraft in fetuses older than 13 to 16 weeks and may provide insights into fetal liver transplantation. Bone Marrow Transplantation (2000) 25, 135-141.

CD8 Antigens↗

PubMed2000

Ligand-specific alphabeta and gammadelta T cell responses in childhood tuberculosis.

The alphabeta and gammadelta T cell responses were analyzed in the peripheral blood of children affected by active tuberculosis (TB) and in healthy children who tested positive (PPD+) or negative (PPD-) for purified protein derivative. PPD+ healthy and diseased children responded equally well to PPD in vitro. In contrast, only 18% of PPD+ TB patients responded to peptide p38G derived from the 38-kDa protein of Mycobacterium tuberculosis. Analysis of the whole gammadelta T cell population and of its Vgamma9/Vdelta2 subset showed similar frequencies in PPD+ children with TB and in healthy PPD+ and PPD- children. Vgamma9/Vdelta2 cells from children with TB responded to 5 different phosphoantigens similarly to those from healthy PPD+ children, but healthy PPD- children responded very poorly. Chemotherapy had contrasting effects on the tested lymphocyte population, represented by increase of alphabeta and decline of Vgamma9/Vdelta2 T cell responses. T cell responses in childhood TB may be similar to those in adult TB.

Adolescent↗

PubMed1999

Broad clonal heterogeneity of antigen-specific CD4+ T-cells localizing at the site of disease during tuberculosis.

The repertoire of CD4+ T-lymphocytes was investigated in six patients affected by tuberculosis, who had a negative PPD skin test at diagnosis. Polyclonal CD4+ T-cell lines from the peripheral blood failed to proliferate to PPD and to the 16- or 38-kDa proteins of Mycobacterium tuberculosis, while CD4+ T-cell lines from the site of disease responded to PPD, and to the 16- and 38-kDa proteins, and derived epitopes in vitro. The repertoire of CD4+ T-cells accumulating at the site of disease was found to be widely heterogeneous as demonstrated by the finding that at least seven different peptides from the 16- and 38-kDa proteins were recognized by every patient. These results indicate that CD4+ T-cells localized at the site of disease in tuberculosis recognize a vast array of M. tuberculosis epitopes.

Amino Acid Sequence↗

PubMed1999

Different role of human HLA-DR and -DQ molecules in xenogeneic transplantation using transgenic mice.

BACKGROUND: The role of T lymphocytes in graft rejection in xenotransplantation is still unclear. The ability of the human HLA class II molecules DR and DQ to function as xenoantigens was investigated in a murine model of skin grafting, using HLA-DR1 and -DQ6-transgenic mice. METHODS: Skin from HLA-DR1- or -DQ6-transgenic mice was transplanted in control littermates. Spleen cells from donors or recipients were tested in mixed lymphocyte reaction and cytotoxic assay. RESULTS: Skin from HLA-DR1-transgenic mice was rejected and spleen cells from rejecting mice were able to proliferate to donor cells, although no rejection was observed when the skin of HLA-DQ6-transgenic mice was engrafted in control littermates. No cytotoxicity was observed in any models. CONCLUSIONS: Taken all together these results clearly suggest a hierarchy in the xenogeneic potency of human HLA class II molecules, with the HLA-DR1 molecule functioning as a potent xenoantigen when compared with the HLA-DQ6 molecule.

Animals↗

PubMed1999

Induction and tolerization of anti-male CD8+ cytotoxic T lymphocytes by in vivo immunization with an H-Y-derived peptide.

We have analyzed the immune response induced by a 9mer synthetic peptide derived from the male histocompatibility antigen H-Y and containing Db-binding motifs in C57BL/6 mice. In this study we report that a single, subcutaneous injection of the peptide emulsified in IFA gave rise to the development of male-specific CD8+ T cells which displayed H-Y-specific proliferative response in vitro and showed a Tc1-type pattern of cytokine production (i.e. they secreted IFN-gamma and IL-2, but not IL-4 and IL-10). Development of a strong cytotoxic activity required in vitro stimulation with specific peptide and IL-2: under these culture conditions, we were able to generate potent CD8+ CTLs that lysed both male cells and peptide-pulsed female cells. Continuous administration of soluble peptide, delivered over a 7-day period by a mini-osmotic pump implanted subcutaneously, inhibited proliferative and cytotoxic responses and IFN-gamma production in lymph node cells from C57BL/6 mice subsequently primed with peptide in adjuvant. This decreased responses were associated with a strong increase in the secretion of IL-4 by antigen-specific CD8+ T lymphocytes. Subcutaneous administration of the H-Y-peptide in adjuvant significantly accelerates rejection of male skin graft, while continuous administration of peptide in soluble form did not modify the time course of rejection.

Animals↗

PubMed1999

Impaired contact hypersensitivity to trinitrochlorobenzene in interleukin-4-deficient mice.

We have examined the role of endogenously produced interleukin-4 (IL-4) in the contact hypersensitivity (CH) reaction to the haptene trinitrochlorobenzene (TNCB). The CH reaction was abolished in IL-4 genetically deficient mice (IL-4 KO), when compared to wild-type (wt) mice. The CH reaction was restored by treatment with IL-4 and further analysis revealed that IL-4 exerted its action both at the induction and effector stages of the CH reaction. Despite failure to develop a CH reaction, IL-4 KO mice developed a T helper type 1 (Th1) response to TNCB, in terms of lymphokine production in vitro. Furthermore, the number of Vgamma3+ cells accumulating in the lymph nodes of TNCB-immune IL-4 KO mice was normal. The recruitment of mononuclear cells and vascular leakage at the challenge site were consistently reduced in IL-4 KO mice and were restored by injection of IL-4. This suggests that IL-4 acts as a proinflammatory mediator in CH, perhaps favouring the accumulation of mononuclear cells at the site of inflammation. Among Th2-type cytokines, IL-13, but not IL-10, was shown to restore the CH reaction to TNCB in IL-4 KO mice. However, IL-4 KO mice developed a normal CH response to oxazolone, indicating that IL-4 was required for the CH reaction to TNCB, but not for that to oxazolone.

Adjuvants, Immunologic↗

PubMed1999

Selection of distinct Valpha/beta T-cell receptor families during in vivo and in vitro T-cell maturation.

The experimental conditions influencing the use of Valphabeta TCR families were examined in lymph node (LN) cells from peptide-immunized C57BL/6 and Vbeta8.2 transgenic mice. Expanded proportions of Vbeta5, Vbeta8.2, Vbeta9, Vbeta12 and Vbeta14 positive cells and an association of Vbeta8.2 with Valpha11 was found in freshly harvested 8-day or 34-day immune LN cells. In contrast, peptide-specific T-cell lines generated in vitro from 8-day immune lymph node cells were found to be almost exclusively of the Valpha2/Vbeta12 family. However, T-cell lines originating from Vbeta8.2 transgenic mice did not show preferential Valpha usage. Anti-Vbeta8.2 antibody produced different effects: when added to cultures of LN cells from C57BL/6 or Vbeta8.2 transgenic strains, the peptide-induced proliferation was suppressed; however, following the injection of mice, subsequent in vitro proliferation and cytokine production induced by both peptide and Concanavalin A was suppressed in Vbeta8.2 transgenic, but much less in C57BL/6 mice. Hence, compensatory expansion of different Vbeta gene products occurred in vivo, but not under the employed in vitro conditions. In conclusion, these results suggest that the TCR family usage is influenced by the experimental conditions in which the T cells are selected and expanded and by the genetic potentials of the precursor pool.

Amino Acid Sequence↗

PubMed1999

Sequestration of T lymphocytes to body fluids in tuberculosis: reversal of anergy following chemotherapy.

The specificity of CD4 T lymphocytes was investigated in 6 patients affected by tuberculosis who had negative tuberculin purified protein derivative (PPD) skin tests at diagnosis. Polyclonal CD4 T cell lines from the peripheral blood failed to proliferate to PPD and to the 16- or 38-kDa proteins of Mycobacterium tuberculosis, while CD4 cell lines from the disease site responded to PPD and to the 16- and 38-kDa proteins and derived epitopes in vitro. Four months after chemotherapy, the patients became responsive to PPD. The proliferative response to PPD and to the 16- or 38-kDa proteins and their derived peptides decreased in CD4 T cell lines from the disease site and increased in lines from the peripheral blood. These results indicate that CD4 T cells recognizing a vast array of M. tuberculosis epitopes are compartmentalized at the site of disease in anergic patients but appear in peripheral blood after chemotherapy.

Antigens, Bacterial↗

PubMed1999

Predominance of Vgamma9/Vdelta2 T lymphocytes in the cerebrospinal fluid of children with tuberculous meningitis: reversal after chemotherapy.

BACKGROUND: We analyzed the gammadelta T cell composition and responses in the peripheral blood and cerebrospinal fluid (CSF) of children affected by tuberculous meningitis (TBM) and in control children. MATERIALS AND METHODS: Peripheral blood and CSF samples were stimulated with different phosphoantigens and IL-2, and expansion of Vgamma9/Vdelta2 T cells assessed by FACS analysis. Vgamma9/Vdelta2 lines were obtained by culturing CSF or peripheral blood mononuclear cells (PBMC) in vitro with phosphoantigens and IL-2 for 2 months, and tested for proliferation and cytokine production in response to phosphoantigens. Vdelta2(D)Jdelta junctional sequence length was assessed by PCR. RESULTS: The repertoire of gammadelta T cells from the CSF of TBM patients was characterized by the predominance of Vgamma9/Vdelta2 T lymphocytes, which accounted for >80% of gammadelta T cells. Vgamma9/Vdelta2 cells from the CSF of TBM children responded to different synthetic and natural (mycobacterial) phosphoantigens and produced discrete amounts of IFN-gamma and TNF-alpha. The in vitro expansion of Vgamma9/Vdelta2 T cells from CSF and peripheral blood of TBM patients prominently decreased following chemotherapy, and similarly, the proportion of ex vivo unstimulated Vgamma9/Vdelta2 T cells in CSF of TBM patients decreased to levels detected in the CSF of control subjects. Vdelta2 CDR3 TCR analysis showed that the remaining Vdelta2 cells in the CSF of TBM patients were still polyclonal. CONCLUSIONS: These findings are consistent with an involvement of Vgamma9/Vdelta2 T cells in TBM. http://link. springer-ny.com/link/service/journals/00020/bibs/5n5p301. html

Antigens↗

PubMed1999

In vivo gammadelta T cell priming to mycobacterial antigens by primary Mycobacterium tuberculosis infection and exposure to nonpeptidic ligands.

BACKGROUND: The recognition of phosphorylated nonpeptidic microbial metabolites by Vgamma9Vdelta2 T cells does not appear to require the presence of MHC molecules or antigen processing, permitting rapid responses against microbial pathogens. These may constitute an important area of natural anti-infectious immunity. To provide evidence of their involvement in immune reactivities against mycobacteria, we measured the responsiveness of peripheral blood Vgamma9Vdelta2 T cells in children with primary Mycobacterium tuberculosis (MTB) infections. MATERIALS AND METHODS: Peripheral blood mononuclear cells from 22 children with MTB infections and 16 positivity of tuberculin (PPD)-negative healthy children were exposed to nonpeptidic antigens in vitro and the reactivity of the Vgamma9Vdelta2 T cell subset with these antigens was determined using proliferation and cytokine assays. Also, responses of gammadelta T cells from rhesus monkeys stimulated with phosphoantigens in vivo were measured. RESULTS: The Vgamma9Vdelta2 T cell responses were highly increased in infected children in comparison with age-matched controls. This augmented Vgamma9Vdelta2 T cell reactivity subsided after successful antibiotic chemotherapy, suggesting that persistent exposure to mycobacterial antigens is required for the maintenance of gammadelta T cell activation in vivo. The in vivo reactivity of Vgamma9Vdelta2 T cells to phosphoantigens was also analyzed in a rhesus monkey model system. Intravenous injections of phosphoantigens induced an activated state of simian Vgamma9Vdelta2 T cells which decreased after 2 months, i.e., with a time course similar to that seen in MTB-infected children. CONCLUSIONS: The increased reactivity of Vgamma9Vdelta2 T cells to phosphoantigens appears to be dependent on constant antigenic exposure. Consequently, the assessment of Vgamma9Vdelta2 responses may be useful for monitoring the efficacy of antimycobacterial therapies.

Animals↗

PubMed1998

The effect of cyclosporin A, FK506 and rapamycin on the murine contact sensitivity reaction.

We have evaluated the effects of three potent immunosuppressive agents, cyclosporin A (CsA), FK506 and rapamycin, on the murine contact sensitivity (CS) reaction to the hapten trinitrochlorobenzene. Development of CS reaction requires participation of three distinct T cell subsets: alphabeta+, CD4+ T lymphocytes, which are the classical effector cell of the CS reaction, gammadelta+ T lymphocytes, and alphabeta+, double-negative (CD4- CD8-) T lymphocytes that express the B220 molecule and produce IL-4. We found that all three drugs inhibit the development of the CS reaction, but they affect different target cells. In fact, rapamycin and FK-506 block both alphabeta+, CD4+ and gammadelta+ T lymphocytes, while CsA inhibits only the alphabeta+, CD4+ T lymphocyte. None of the three drugs exerted any inhibitory activity on the alphabeta+, double-negative (CD4- CD8-) T lymphocytes. Hapten-immune lymph node cells from mice treated in vivo with CsA or FK506 failed to proliferate and to produce IL-2 when re-exposed to the specific antigen in vitro. In contrast, immune lymph node cells from mice that had been treated in vivo with rapamycin gave optimal antigen-specific proliferation and IL-2 production in vitro. The implications of these observations are discussed in relation to the use of these immunosuppressive agents for prevention of allograft rejection.

Animals↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗