Biomedical subjects

D Olive

Publications and source records attributed to D Olive.

At least 73 records · Page 4Linked to original sources

PubMed1999

HOX gene expression is altered in the endometrium of women with endometriosis.

HOXA10 and HOXA11 are homeobox genes that function as transcription factors essential to embryonic development. We have recently described a role for each of these two genes in regulating endometrial development in the adult during the course of a menstrual cycle. Both Hoxa10 and Hoxa11 are essential for implantation in the mouse and appear to play a similar role in women. To investigate the role of HOX genes in the endometrium of women with endometriosis, quantitative Northern blot analysis was performed on the endometrium of 40 normal cycling controls and 40 patients with documented endometriosis. Patients with endometriosis failed to show the expected mid-luteal rise in HOX gene expression as demonstrated in the controls. Aberrant HOX gene expression suggests that altered development of the endometrium at the molecular level may contribute to the aetiology of infertility in patients with endometriosis.

Adult↗

PubMed1999

Treatment of chronic myelogenous leukemia with interleukin-2: a phase II study in 21 patients.

We designed a phase II study to assess the activity of recombinant interleukin-2 (rIL-2) in patients with chronic myelogenous leukemia (CML). Study population included 11 patients in the chronic phase of CML (6 in hematologic remission and 5 with active disease), 6 patients in the accelerated phase, and 4 in blastic phase of CML. Patients received three 5-day cycles administrated every other week. rIL-2 was given as intravenous bolus infusions of 8 x 10(6) IU/m2 three times a day during cycle 1 and twice a day during cycles 2 and 3. Response to rIL-2 was assessed on day 45. No hematologic response was achieved in the patients with evaluable disease. One patient in hematologic remission with rIL-2 achieved a major response (from 72% to 9% Ph+ metaphases), and two patients had some degree of reduction of Ph+ metaphases. Responses were short-lived (< 6 months), but two of these three patients achieved a new cytogenetic response with interferon given post-rIL-2. A significant immune activation was achieved with rIL-2 including a marked increase in CD3+/CD25+ cells, CD56+ cells, and in natural killer/lymphokine activated killer cell cytotoxic activity. These results confirm preclinical studies, which showed that IL-2 has antileukemic activity in CML. However, the responses observed were short lived and restricted to a subgroup of patients with low disease burden. This invites further studies testing its impact in situations of minimal disease or in combination with other cytokines.

Adolescent↗

PubMed1999

Interaction of Brucella abortus lipopolysaccharide with major histocompatibility complex class II molecules in B lymphocytes.

Lipopolysaccharide (LPS), a major amphiphilic molecule located at the outer membrane of gram-negative bacteria, is a potent antigen known to induce specific humoral immune responses in infected mammals. LPS has been described as a polyclonal activator of B lymphocytes, triggering the secretion of antibodies directed against distinct sugar epitopes of the LPS chain. But, how LPS is handled by B cells remains to be fully understood. This task appears to be essential for a better knowledge of the anti-LPS humoral immune response. In this study, we examine the internalization of LPS and its interaction with antigen-presenting major histocompatibility complex (MHC) class II molecules in murine and human B-cell lines. By use of immunofluorescence, we observe that structurally different LPSs from Brucella and Shigella strains accumulate in an intracellular compartment enriched in MHC class II molecules. By use of immunoprecipitation, we illustrate that only Brucella abortus LPS associates with MHC class II molecules in a haplotype-independent manner. Taken together, these results raise the possibility that B. abortus LPS may play a role in T-cell activation.

Animals↗

PubMed1999

Simian immunodeficiency virus and human immunodeficiency virus type 1 nef proteins show distinct patterns and mechanisms of Src kinase activation.

The nef gene from human and simian immunodeficiency viruses (HIV and SIV) regulates cell function and viral replication, possibly through binding of the nef product to cellular proteins, including Src family tyrosine kinases. We show here that the Nef protein encoded by SIVmac239 interacts with and also activates the human Src kinases Lck and Hck. This is in direct contrast to the inhibitory effect of HIV type 1 (HIV-1) Nef on Lck catalytic activity. Unexpectedly, however, the interaction of SIV Nef with human Lck or Hck is not mediated via its consensus proline motif, which is known to mediate HIV-1 Nef binding to Src homology 3 (SH3) domains, and various experimental analyses failed to show significant interaction of SIV Nef with the SH3 domain of either kinase. Instead, SIV Nef can bind Lck and Hck SH2 domains, and its N-terminal 50 amino acid residues are sufficient for Src kinase binding and activation. Our results provide evidence for multiple mechanisms by which Nef binds to and regulates Src kinases.

Amino Acid Sequence↗

PubMed1999

Tumor escape from immune surveillance.

The bases for an efficient anti-tumor immune response begin to be better defined. Nonetheless, neoplastic cells develop various strategies to escape immune surveillance, which are discussed here in order to better design the therapeutic possibilities of immune manipulation. The absence of specific tumor antigen as well as the weak expression of major histocompatibility complex (MHC) molecules hinder the recognition of the neoplastic cells by T lymphocytes. The defect of expression by the tumor of the ligands for the T cell activation costimulatory molecules is particularly harmful for the immune response since it induces tolerance. Finally, tumor cells can inactivate effector T lymphocytes through the secretion of inhibitory cytokines, induction of apoptosis or functional inactivation. The multiplicity of the means to oppose an effective anti-tumor response challenges the adaptative mechanisms of the immune system. For example, the natural killer cells target tumor cells not expressing MHC class I molecules. Numerous possibilities of tumor immunogenicity restoration have been demonstrated at least in vitro, such as stimulation of the cancerous cells by CD40 or cytokine treatment, which could lead to several promising therapeutical approaches.

Humans↗

PubMed1999

Differential modulation of immune recognition molecules by interleukin-7 in human acute leukaemias.

Clinical animal models and in vitro data afford evidence for anti-leukaemia immunity. Many reports have underlined the interest of interleukin-7 (IL-7) use in cancer and its pivotal role in immune recognition. This cytokine, initially identified as a B cell growth factor, enhances the anti-tumour properties of immune effector cells via T lymphocyte activation, increased specific cytotoxicity and cytokine secretion. Nonetheless, few data are available regarding the effect of IL-7 on the expression at the leukaemia cell surface of molecules involved in the immune response, which defective expression could induce tolerance or anergy. This prompted us to study the effects of IL-7 on 20 cases of acute myeloid leukaemia (AML) and 9 cases of lymphoid leukaemia (ALL), in comparison with gamma-interferon, a potent inducer of immune regulation molecule expression. In AML and ALL, IL-7 increased MHC class I molecule expression, while class II molecules were weakly modified. The expression of the tumour necrosis factor family members CD40 and Fas/CD95, together with the adhesion molecules ICAM-1/CD54 and CD58/LFA-3, was also increased in both types of leukaemia. The IL-7 was an efficient inducer of B7-2/CD86 expression in AML and ALL, while increased expression of B7-1/CD80 was only observed in AML. In the corresponding, co-cultured T lymphocyte population, IL-7 more particularly increased B7-1/CD80 and CD58/LFA-3 expression. Finally, pre-incubation of leukaemic cells with IL-7 increased the proliferation of responding, normal allogenic T lymphocytes and their secretion of gamma-IFN and IL-2 in mixed the lymphocyte-tumour reaction. We concluded that IL-7 is efficient at increasing the membrane expression of molecules which are central for the development of the immune response, and at improving allogenic immune recognition. The clinical implications of such data require further in vivo investigation.

Antigens, CD↗

PubMed1999

Guidelines for the diagnosis and treatment of hyperprolactinemia.

Hyperprolactinemia is the most common endocrine disorder of the hypothalamic-pituitary axis. While it can occur in men, it occurs more commonly in women. The prevalence of hyperprolactinemia ranges from 0.4% in an unselected normal adult population to as high as 9-17% in women with reproductive disorders. There are many possible causes of hyperprolactinemia, falling into three general categories: physiologic, pharmacologic and pathologic. When specific treatable underlying causes have been eliminated and in cases of severe hyperprolactinemia, the most likely cause is a prolactin (PRL)-secreting pituitary adenoma. Microadenomas should be treated medically, with a dopamine agonist, if there is an indication for therapy (such as amenorrhea, infertility or bothersome galactorrhea). If there is no indication for therapy, microadenomas may be followed conservatively, as growth is uncommon. Macroadenomas may grow larger; medical therapy is recommended initially, with neurosurgical evaluation reserved for specific clinical situations, such as failure of medical therapy and evidence of mass effect despite medical therapy. In the United States, the dopamine agonists indicated for treatment of hyperprolactinemia are bromocriptine and cabergoline. Bromocriptine is usually given once or twice daily, while cabergoline has a long duration of action and is given once or twice weekly. Results of comparative studies indicate that cabergoline is clearly superior to bromocriptine in efficacy (PRL suppression, restoration of gonadal function) and tolerability.

Adult↗

PubMed1999

Indications for hyperprolactinemia therapy.

Before initiating treatment for hyperprolactinemia, it is necessary to verify the diagnosis. It is also essential to remember that hyperprolactinemia is in itself simply an abnormal "lab value" that reflects the presence of an underlying pathophysiologic cause. All possible causes must be considered and either identified or ruled out before therapy is initiated. The vast majority of people with hyperprolactinemia can be treated medically with dopamine agonist medications. The indications for treatment include: (1) the presence of significant symptoms, such as infertility, ovulatory dysfunction or galactorrhea in women and infertility or gynecomastia in men; (2) the presence of significant signs, such as visual field defects or cranial nerve palsies; and (3) abnormal test results, including visualization of a pituitary mass or lesion or detection of osteopenia.

Adult↗

PubMed1998

Distinct regulation of T-cell death by CD28 depending on both its aggregation and T-cell receptor triggering: a role for Fas-FasL.

CD28 is a major coreceptor that regulates cell proliferation, anergy, and viability of T cells. The negative selection by T-cell receptor (TCR)-induced cell death of immature thymocytes as well as of activated human antigen-specific T-cell clone, requires a costimulatory signal that can be provided by CD28. Conversely, CD28-mediated signals increase expression of Bcl-XL, a survival gene, and promote survival of naive T cells cultured in the absence of antigen or costimulation. Because CD28 appears to both protect from, or induce T-cell death, one important question is to define the activation and cellular parameters that dictate the differential role of CD28 in T-cell apoptosis. Here, we compared different CD28 ligands for their ability to regulate TCR-induced cell death of a murine T-cell hybridoma. In these cells, TCR triggering induced expression of Fas and FasL, and cell death was prevented by anti-Fas blocking monoclonal antibody (MoAb). When provided as a costimulus, both CD28 MoAb and the B7.1 and B7.2 counter receptors downregulated, yet did not completely abolish T-cell receptor-induced apoptosis. This CD28 cosignal resulted in both upregulation of Bcl-XL and prevention of FasL expression. In marked contrast, when given as a single signal, CD28 MoAb or B7.1 and B7.2 induced FasL expression and resulted in T-cell death by apoptosis, which was dependent on the level of CD28 ligation. Furthermore, triggering of CD28 upregulated FasL and induced a marked T-cell death of previously activated normal peripheral T cells. Our results identify Fas and FasL as crucial targets of CD28 in T-cell death regulation and show that within the same cell population, depending on its engagement as a single signal or as a costimulus together with the TCR, CD28 can either induce a dose-dependent death signal or protect from cell death, respectively. These data provide important insights into the role of CD28 in T-cell homeostasis and its possible implication in neoplastic disorders.

Animals↗

PubMed1998

The human immunodeficiency virus type 1 Nef protein binds the Src-related tyrosine kinase Lck SH2 domain through a novel phosphotyrosine independent mechanism.

Primate lentiviruses encode for an unique nef gene with an essential function in both viral replication and pathogenicity in the host. The molecular basis for this function remains however poorly defined. Several Nef-binding cellular proteins are thought to be instrumental in its function. Indeed, Nef contains a proline-rich motif implicated in the binding to the Src-like tyrosine kinase Hck and also to a Ser/Thr kinase of molecular weight 62 kDa. The disruption of this motif affects the binding to both these kinases as well as viral replication. Whereas Hck is expressed in the myeloid lineage and hence may account for the nef function in infected monocytes, we and others have reported previously that Nef also interacts with the T-lymphocyte Src-kinase Lck, leading to specific cell signaling impairment. This interaction occurs through the binding of Nef to both Lck SH2 and SH3 domains. Both the proline motif and phosphorylation of Nef on tyrosine residue were proposed to account for these interactions. Here, we investigate the mechanism of Lck SH2 binding by HIV-1 Nef. Using recombinant fusion proteins to precipitate lysates, we show that although SH2 binding is dependent on phosphorylation events, it occurs in a tyrosine independent manner because it requires neither tyrosine residues in Nef nor the phosphotyrosine binding pocket from the Lck SH2 domain, hence suggesting a role for a phosphoserine or a phosphothreonine residue. Further, we show that Hck SH2 does not interact with Nef, indicating that Hck SH3 binding is sufficient for Nef binding, whereas Lck SH2 cooperate together with SH3 to allow Nef binding to a level similar to Hck SH3. Together, our results establish different mechanisms for Hck and Lck binding by HIV-1 Nef protein, and identify a novel mechanism for Src-like tyrosine kinase targeting by a viral protein.

Gene Products, nef↗

PubMed1998

HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium.

Hox genes are well-known transcriptional regulators that play an essential role in directing embryonic development. Mice that are homozygous for a targeted disruption of the Hoxa10 gene exhibit uterine factor infertility. We have recently demonstrated that HOXA10 is expressed in the adult human uterus. To examine expression of HOXA10 during the menstrual cycle, Northern blot analysis and in situ hybridization were performed. Expression of HOXA10 dramatically increased during the midsecretory phase of the menstrual cycle, corresponding to the time of implantation and increase in circulating progesterone. Expression of HOXA10 in cultured endometrial cells was stimulated by estrogen or progesterone. Stimulation of HOXA10 by progesterone was concentration-dependent within the physiologic range, and the effect of estrogen was inhibited by cycloheximide. These results identify sex steroids as novel regulators of HOX gene expression. HOXA10 may have an important function in regulating endometrial development during the menstrual cycle and in establishing conditions necessary for implantation in the human.

Cells, Cultured↗

PubMed1998

Regulation of CD80/B7-1 and CD86/B7-2 molecule expression in human primary acute myeloid leukemia and their role in allogenic immune recognition.

Clinical data and animal models afford evidence for anti-leukemia immunity in humans, but the interactions critical for blast cell recognition are unresolved. Expression of B7 molecules by antigen-presenting cells (APC) provides co-stimulatory signals to T lymphocytes via CD28 and CTLA-4 which prevent the induction of alloantigen-specific tolerance. Conversely, expression of CD40 ligand by stimulated T cells activates APC via CD40. In human hematological B cell malignancies (follicular lymphoma and chronic lymphocytic leukemia), the defect in alloantigen presentation of tumoral cells can be repaired by up-regulation of B7 and other co-stimulatory molecules via CD40. We studied the role of B7 molecules in alloimmune recognition and the various ways to improve the antitumoral response on peripheral blood leukemic cells from 20 patients with a diagnosis of primary acute myeloid leukemia (AML). We focused on myelo/monocytic M4/M5 French-American-British classification subtypes which are considered as the neoplastic counterpart of normal monocytes, a prototypic APC. In one-way mixed lymphocyte reaction of CD4+ T cells against leukemic cells, differences in B7-1, B7-2 or CD40 expression by AML cells did not induce specific cytokine secretion; interleukin (IL)-2 and interferon (IFN)-gamma were detected but not IL-4, corresponding to a Th1 pattern. Blockade experiments showed that proliferation and IFN-gamma secretion only partially depended on B7 molecules, which in contrast had a pivotal role in IL-2 synthesis. In contrast with murine models which suggest a pivotal role for CD80/B7-1 in the immune response against AML, our data support a greater role for CD86/B7-2, in line with the baseline expression of CD86/B7-2 and lack of CD80/B7-1 on most M4/M5 AML cells. AML cell stimulation via CD40: (1) significantly improved IL-2 secretion but not proliferation of responding T lymphocytes, (2) increased CD54/ICAM-1 expression in three quarters of cases, (3) failed in most cases to induce CD40-specific CD80/B7-1 up-regulation, and (4) had a weak effect on CD86/B7-2 expression. These data contrast with the very efficient up-regulation of both B7 co-stimulatory molecule expression and tumoral cell alloimmune recognition following CD40 stimulation in B cell malignancy models. The role of the defective B7 molecule up-regulation by the CD40 pathway in inefficient tumor immunogenicity of primary AML cells has to be further investigated, in particular using transfection experiments of CD80/B7-1-deficient AML cell lines. From our in vitro data we conclude that B7 molecules play an important role in the alloimmune surveillance of AML as suggested by the high B7 molecule dependency of IL-2 secretion. Nonetheless, the contribution of B7 molecules to alloimmune T cell proliferation against primary AML cells in human and the way to improve it--regulation via CD40 in particular--differ from B cell malignancies and murine models, suggesting the requirement for specific strategies in the development of antitumor immunity.

Antigen Presentation↗

PubMed1998

High implantation and pregnancy rates with transfer of human blastocysts developed in preimplantation stage one and blastocyst media.

OBJECTIVE: To evaluate the proficiency of preimplantation stage one (P1) and blastocyst media in supporting human blastocyst development and to document implantation and clinical pregnancy rates from the transfer of the normally developed blastocysts. DESIGN: Retrospective clinical study. SETTING: Private IVF unit of a university-affiliated center. PATIENT(S): Twenty-eight women aged 33.7 +/- 2.9 years who underwent IVF treatment for infertility. INTERVENTION(S): Bipronucleate oocytes obtained from IVF and intracytoplasmic sperm injection were cultured in vitro with P1 and blastocyst media for 96-120 hours. One to three embryos were transferred (2.1 +/- 0.2 for the patients who became pregnant and 1.5 +/- 0.3 for those who did not become pregnant). MAIN OUTCOME MEASURE(S): Total number and percentage of developed blastocysts, frequency of blastocysts of grades A and B, and implantation and pregnancy rates. RESULT(S): From 431 oocytes retrieved, 269 bipronucleate oocytes were cultured, producing 81 blastocysts that resulted in the transfer of 54 embryos in 27 procedures. Blastocysts developed in 39.7% +/- 5.5% of the pregnant group and 30.2% +/- 4.5% of the nonpregnant group. From 15 (15/27 = 55.6%) clinical pregnancies, 18 (18/54 = 33.3%) gestational sacs were visualized. The rate of implantation in the pregnant group was 58.1% (18/31). CONCLUSION(S): These results provide evidence for the benefits of extending human embryo culture with P1 and blastocyst media for all normally fertilized embryos in vitro.

Adult↗

PubMed1998

[Hodgkin's disease in patients infected with the human immunodeficiency virus].

INTRODUCTION: Hodgkin's disease in patients infected by the human immunodeficiency virus (HIV) is still not part of the definition of acquired immune deficiency syndrome. Nonetheless, this entity has a particular presentation when compared to the disease occurring in immune-competent patients. CURRENT KNOWLEDGE AND KEY POINTS: Increased frequency (> 75%) of advanced anatomical stages and extranodular localizations (Ann Arbor system stages III and IV) has been outlined in HIV-infected patients. Mediastinal involvement is more unusual in immunocompromised than in immune-competent patients. The presence of B symptoms (fever, weight loss, nocturnal sweats) is very frequent. Finally, the predominance of mixed cellularity (type 3) characterizes Hodgkin's disease in immunocompromised patients. Due to either the immunodeficiency, antiretroviral treatments, poor hematological tolerance in response to chemotherapy, or to advanced anatomical stages, disease management may be hampered. Current therapeutical approaches often obtain complete remission; however, some deaths are still related to the disease progression to acquired immune deficiency syndrome. FUTURE PROSPECTS AND PROJECTS: From these observations, Hodgkin's disease management in HIV-infected patients relies on therapeutical approaches similar to those used for non infected patients, with some specific recommendations. Chemotherapy should be conducted in the shortest time in order to minimize chemotherapy-induced immunosuppression. Simultaneous use of antiretroviral treatment and reinforced opportunistic infection prophylaxis are of pivotal importance. Finally, the use of hematopoietic growth factors appears to be safe regarding viral replication, but still requires further evaluation.

AIDS-Related Opportunistic Infections↗

PubMed1998

Malignant plasma cell lines express a functional CD28 molecule.

The function of CD28 molecules that are present on malignant plasma cells of human myeloma cell lines (HMCL) was studied. First, myeloma cells expressed a similar density of CD28 antigen to that of normal T cells. The myeloma CD28 molecules were able to bind B7-Ig molecules as well as L cells transfected with a B7-1 cDNA, and anti-CD28 mAb inhibited the binding. Myeloma cells did not express B7-1 antigens but a low density of B7-2 antigens. The myeloma B7-2 molecules of two HMCL were able to bind CTLA-4 protein. No autocrine CD28:B7-2 activation could be evidenced as we found no spontaneous binding of the p85 subunit of PI-3 kinase to CD28 molecules. In addition, a blocking anti-CD28 mAb did not affect the IL-6-dependent or autonomous proliferation of the HMCL. The activation of myeloma CD28 molecules with or without TPA stimulation did not affect the proliferation, survival, differentiation, expression of activation antigens and cytokine receptors or cytokine production of myeloma cells. However, the triggering of myeloma CD28 molecules by B7-1 transfectant cells resulted in binding of the p85 subunit of PI-3 kinase to CD28 molecules as previously shown for T cell CD28 molecules. This expression of a large density of CD28 molecules able to bind B7 molecules might contribute to a downregulation of the immune control of myeloma cells.

B7-1 Antigen↗

PubMed1998

PRAME, a gene encoding an antigen recognized on a human melanoma by cytolytic T cells, is expressed in acute leukaemia cells.

Gene PRAME was found to encode an antigen recognized on a human melanoma cell line by an autologous cytolytic T-lymphocyte clone. This gene is expressed at a high level in a very large fraction of tumours, such as melanomas, non-small-cell lung carcinomas, sarcomas, head and neck tumours and renal carcinomas. It is therefore a candidate for tumour immunotherapy even though some low expression is found in certain normal tissues. We tested by RT-PCR the expression of PRAME on more than 250 bone marrow or blood samples from patients with a haematological malignancy. Approximately 25% of the acute leukaemia samples were positive. Remarkably, all acute myeloblastic leukaemias that carried the chromosomal translocation t(8;21), which fuses the genes AML1 and ETO, expressed PRAME at a high level.

Acute Disease↗

PubMed1998

Two distinct regions of the CD28 intracytoplasmic domain are involved in the tyrosine phosphorylation of Vav and GTPase activating protein-associated p62 protein.

The T cell-associated CD28 molecule plays a key role in T cell co-stimulation. Its ligation induces the tyrosine phosphorylation of numerous proteins including CD28 itself as well as a restricted set of substrates of 97 and 62-68 kDa which are poorly phosphorylated by the tyrosine kinases induced by CD3-TCR triggering. In this study, we identify these substrates as the product of the vav proto-oncogene and as a 62 kDa protein that could correspond at least in part to p62dok, the 62 kDa adaptor molecule associated to p120 Ras-GTPase activating protein. Both p97vav and p62 are tyrosine phosphorylated upon CD28 ligation by mAb or by its counter-receptor B7-1/CD80. Using CD28 mutants, we also show that Vav and p62 tyrosine phosphorylation is regulated by distinct domains within the CD28 cytoplasmic tail: residues 173-181 for Vav and residues 182-202 for p62. Finally, the phosphorylation of Vav and p62 does not require an intact binding site for Grb-2 or p85 SH2 domains. We thus demonstrate that the CD28 cytoplasmic domain contains at least three functionally independent regions involved in CD28-induced signal transduction, since in addition to the Grb-2 and p85 SH2 domain binding site (Tyr173), residues 173-181 and 182-202 are associated with Vav and p62 tyrosine phosphorylation respectively.

Animals↗

PubMed1998

B7.1 costimulatory molecule is expressed on thyroid follicular cells in Hashimoto's thyroiditis, but not in Graves' disease.

The molecules of the B7 family play a major role in T-lymphocyte costimulation through interaction with their counterreceptors CD28 and CTLA4. In the present study, we analyzed the possible expression of B7 molecules on surgically removed thyroid tissue of patients with autoimmune [Hashimoto's thyroiditis (HT) or Graves' disease (GD)] or nonautoimmune [nontoxic goiter (NTG) or papillary cancer (PC)] thyroid diseases. We found clear positivity of thyroid follicular cells for B7.1 in HT but not in GD, nor in nonautoimmune specimens (NTG, PC) using in situ analysis by alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. Double immunostaining experiments in combination with an anti-human thyroglobulin antibody confirmed follicular B7.1 localization. On the contrary, no follicular B7.2 expression was observed in any specimen analyzed. These findings were confirmed by immunofluorescence flow cytometry on isolated follicular cells. The cytokines IL1beta and LPS were able to induce de novo B7.1 expression on cultured thyroid follicular cells. Intrathyroid T cells proved responsive to stimulation via the B7 ligand CD28, even in the absence of IL2. Moreover preliminary evidence was obtained for an inhibitory effect of anti-B7.1 mAb on T-cell proliferation in coculture with isolated thyroid follicular cells. It is conceivable that in HT, expression of B7.1 on follicular cells, together with MHC class II antigens and ICAM1, could provide a local costimulatory signal for T-lymphocyte differentiation toward the type 1 cytokine secretion pattern and maintenance of the autoimmune process.

Adult↗