Secondary aneurysmal bone cyst in Langerhans cell histiocytosis: Case report, literature review.

Langerhans cell histiocytosis (LCH) is a rare disease of the myeloid precursor cells, it predominantly occurs in the skull and long bones as unifocal bone lesions. Aneurysmal bone cysts (ABC) are benign, expansive and lytic bone. Reports of secondary ABC occurring in LCH are rare, having only been reported twice in the skull. Here, we report the first case of LCH masquerading as ABC in a 14-month-old female child who presented with a rapidly growing mass in her left femur. The lesion had typical radiological features of ABC, and only histological examination revealed the presence of cells suggestive of LCH.

Pancake kidney, a rare and often misdiagnosed malformation: a case report and radiological differential diagnosis.

Renal ectopia and fusion anomalies are Congenital Anomalies of the Kidney and the Urinary Tract (CAKUT) that are usually incidentally detected and asymptomatic. Patients affected present a higher risk of complications like recurrent urinary tract infections or obstruction. Pancake kidney (PK) is one of the rarest types of renal anomaly with complete fusion of the superior, mild and inferior poles of both kidneys in the pelvic cavity. Each kidney has its own excretory system with two ureters that do not cross the midline. In the asymptomatic cases, a conservative approach should be performed. Surgical management may be needed when urological problems occur. PK is often associated with congenital anomalies of other organs. Ultrasound is the first line radiological examination for the diagnosis and the follow-up of kidney malformations. The main sonographic findings suggesting PK diagnosis are a large and lobulated renal mass consisting of two fused lateral lobes without an intervening septum located in the pelvic cavity. Each lobe usually has a separate pelvicalyceal system, the renal pelvis is anteriorly placed and the ureters are usually short and enter the bladder normally without crosses the midline. Ultrasonography gives useful information on the morphology and volume of the organ, and on its vascularization through the use of the Color- and Power-Doppler. Computer Tomography and Magnetic Resonance Urography are second level techniques used to confirm the diagnosis and to evaluate the presence of other abnormalities. The knowledge of the imaging findings and the anatomy of congenital renal malformations is important to avoid diagnostic pitfalls and misinterpretations. We report the case of a 14-years old female with PK who was misdiagnosed with a horseshoe kidney (HSK) during an abdominal ultrasound.

Musculoskeletal hydatid disease: report of a rare case with primary and exclusive localization in right hemi-pelvis and femur.

Hydatid Disease (HD), also called Echinococcosis or Hydatidosis, is a parasitic infection caused by the larval stage of the tapeworm Echinococcus: E. granulosus or E. multilocularis. HD occur most frequently in liver or lungs, rarely in brain, skeletal muscles, bones, kidneys, spleen. Bone infestation of Echinococcosis hydatid cysts occurs respectively by haematogenous seeding and progressive invasion into bone by lesions in the adjacent soft tissues. Patients with musculoskeletal HD clinically show the disease in adulthood because the lesions develop very slowly. In some cases, HD is an uncommon cause of soft tissue mass, pain and neurovascular symptoms due to compression or to secondary infection. Diagnostic imaging plays an important role in the diagnosis of HD and in the differential diagnosis with soft tissue tumors. We present a rare case of male patient of 42 year-old with diagnosis of HD with primary and exclusive localization in right hemi-pelvis and femur.

Association of deletion 9p, 46,XY gonadal dysgenesis and autistic spectrum disorder.

Deletions of distal chromosome 9p24 are often associated with 46,XY gonadal dysgenesis and, depending on the extent of the deletion, the monosomy 9p syndrome. We have previously noted that some cases of 46,XY gonadal dysgenesis carry a 9p deletion and exhibit behavioural problems consistent with autistic spectrum disorder. These cases had a small terminal deletion of 9p with limited or no somatic anomalies that are characteristic of the monosomy 9p syndrome. Here, we present a new case of 46,XY partial gonadal dysgenesis and autistic spectrum disorder associated with a de novo deletion of 9p24 that was detected by ultra-high resolution oligo microarray comparative genomic hybridization. The deletion included the candidate sex-determining genes in the region DMRT1 and DMRT3. These data suggest that a gene responsible for autistic spectrum disorder is located within 9p24. It remains to be determined if the gonadal dysgenesis and autistic spectrum disorder are caused by a single gene or if they are caused by distinct genetic entities at 9p24.

Factors associated with climacteric symptoms in women around menopause attending menopause clinics in Italy.

OBJECTIVE: To obtain data on correlates of climacteric symptoms in women around menopause attending menopause clinics in Italy. METHODS: Since 1997 a large cross sectional study has been conducted on the characteristics of women around menopause attending a network of first level menopause outpatient's clinics in Italy. A total of 66,501 (mean age 54.4 years) women are considered in the present paper. RESULTS: The odds ratios of moderate and severe hot flashes/night sweats were lower in more educated women and (for severe symptoms only) in women reporting regular physical activity. Depression, difficulty to sleep, forgetfulness and irritability tended to be less frequent in more educated women and (depression only) in women reporting regular physical activity. Parous women reported more frequently these symptoms. CONCLUSIONS: This large study confirms in Southern European population that low education, body mass index and low physical activity are associated with climacteric symptoms. Parous women are at greater risk of psychological symptoms.

Primary systemic anaplastic large-cell lymphoma (CD30+): advances in biology and current therapeutic approaches.

In 1985, Stein et al demonstrated the expression of the lymphoid activation antigen CD30/Ki by neoplastic cells. Fifteen years after the first description, anaplastic large-cell lymphomas (ALCL) are now thought to be a heterogeneous group in terms of their clinical, morphologic, phenotypic, cytogenetic, and molecular biology features. However, on the basis of a specific genetic anomaly and expression of a chimeric nucleophosmin anaplastic lymphoma kinase (NPM-ALK) protein and its variants, a distinct clinicopathologic entity defined as "ALK-positive lymphoma" or "ALKoma" can be recognized. Based on molecular and clinical criteria, 3 entities of primary ALCL can be identified: primary systemic ALK positive, primary systemic ALK negative, and primary cutaneous ALCL. This review focuses on advances in the knowledge of primary systemic ALCL biology and discusses therapeutic approaches based on ALK expression. The presence of this protein appears to be an important prognostic factor and, combined with an age-adjusted International Prognostic Index, could allow researchers to design more specific clinical trials aimed at finding new, more efficacious and less toxic treatments.

Clinical activity and safety of combination immunotherapy with IFN-alpha 2a and Rituximab in patients with relapsed low grade non-Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: To determine the clinical activity and safety of the combination immunotherapy of the chimeric anti-CD20 antibody, Rituximab, and Interferon (IFN)- alpha 2a DESIGN AND METHODS: Sixty-four patients with relapsed low-grade or follicular B-cell non Hodgkin's lymphoma received 4 infusion of Rituximab (375 mg/m(2) x dose) after priming and simultaneous treatment with IFN- alpha 2a. RESULTS: The overall response rate was 70% with 33% complete responses. Median for duration of response is 19 months, after a median follow-up of 22 months. By univariate analysis none of the most common prognostic factors predicted for response to therapy. After treatment 10 patients become bcl-2 negative in the bone marrow, but no correlation between molecular and clinical response was found. Fifty-three patients (83%) had drug related or unknown origin adverse events. The number of adverse events per patient varied from 1 to 21. Considering all 272 events, 231 (85%) were grade 1 or 2, 36 (13%) grade 3 and 5 (2%) grade 4. Twenty-three patients required reduction in the dose and/or short discontinuation of IFN treatment, either during priming or subsequent treatment. The most frequent adverse events were leukopenia, fever, neutropenia, hypotension and thrombocytopenia. INTERPRETATION AND CONCLUSIONS: this report shows that combination immunotherapy Rituximab + IFN- alpha 2a is active and relatively well tolerated. The overall response rate of 70% and the median duration remission of 19 months compare favorable with the results obtained with Rituximab alone in similar subset of patients. Randomized trials, investigating Rituximab versus combination immunotherapy are needed.

Treatment of B-cell non-Hodgkin's lymphoma with anti CD 20 monoclonal antibody Rituximab.

Rituximab is a chimeric anti CD-20 monoclonal antibody containing human IgG1 kappa constant regions, with murine variable regions. The anti-lymphoma effects of Rituximab are probably due to complement and antibody-dependent cell-mediated cytotoxicity, and induction of apoptosis. Phase II trials have demonstrated a strong activity of rituximab alone in indolent B non-Hodgkin lymphoma, especially in patients with follicular lymphoma. The most utilized dose-schedule is 375 mg/m(2) weekly x 4. The association with chemotherapy or with interferon-alpha increases Rituximab efficacy. More recently, Rituximab have showed activity also in diffuse large cell lymphoma, mantle cell lymphoma and in other B-malignancies. Good results have also been obtained utilizing Rituximab for in vivo purging. However, we are still far from having found a definite position for Rituximab in the treatment of lymphoproliferative disorders. The aim of future studies should be to develop new strategies that will hopefully produce the most effective Rituximab-based regimens in order to find the Rituximab key position in the treatment of B-malignancies

Diagnosis of essential thrombocythemia at platelet counts between 400 and 600x10(9)/L. Gruppo Italiano Malattie Mieloproliferative Croniche(GIMMC).

BACKGROUND AND OBJECTIVE: Diagnostic criteria for essential thrombocythemia (ET) remain essentially negative, that is, exclusion of other myeloproliferative diseases and causes of reactive thrombocytosis. A platelet count above 600x10(9)/L is still generally considered an absolute diagnostic criterion although new protocols for positive diagnostic criteria have recently been proposed, reducing the stringency of a definite platelet limit. This study demonstrates that a platelet count 600x10(9)/L is not a reliable diagnostic criterion for ET, especially in the early stages. DESIGN AND METHODS: An ongoing retrospective study by the GIMMC analyzed 2,316 ET patients diagnosed between 1986 and 1995. Of these 2,316 patients, diagnosed according to the PVSG criteria, 68 had a platelet count 600x10(9)/L and were analyzed separately; 37 out of 68 were excluded from this analysis because of a follow-up shorter than 2 years and/or because of treatment with myelosuppressive agents. The remaining 31 patients were the subjects of our study. RESULTS: After a median follow-up of 4.56 years (range 2-9.6 years) none of the 31 patients had a spontaneous decrease of platelets to the normal range. Transformation to a different chronic myeloproliferative disorders was never observed and no patient developed a condition known to produce reactive thrombocytosis. During follow-up, 23 patients (74%) were treated with anti-aggregating drugs, mainly aspirin. The disease did not evolve into acute leukemia in any patient, 1 had a thrombotic event and none presented hemorrhagic episodes. Median platelet count during follow-up was 534x10(9)/L (range 398-997x10(9)/L). INTERPRETATION AND CONCLUSIONS: Long term follow-up has documented that our 31 patients were correctly diagnosed as having ET, although platelet count was 600x10(9)/L. Our patients were probably in a early phase of their disease and following updated PVSG criteria would have been misdiagnosed leading to incomplete recognition of the natural history of the disease. Further, because an early diagnosis could also have a clinical relevance, our results outline the need for new criteria for the diagnosis of ET. The exclusion of patients with a platelet count between 400 and 600x10(9)/L may prevent patients, nevertheless at risk of vascular complications, from being treated.

Influence of hepatitis G virus coinfection on the clinical course of chronic hepatitis C.

Hepatitis G virus (HGV) is a parenterally transmitted virus, frequently associated with hepatitis C virus infection. Hepatitis G virus RNA was detected by reverse transcription-polymerase chain reaction in the serum of 40 patients with chronic hepatitis C. Nine (22.5%) patients had evidence of hepatitis G virus viraemia. No significant epidemiological or virological differences could be demonstrated between subjects infected with both hepatitis G virus and hepatitis C virus and subjects infected with hepatitis C virus alone. Aminotransferase values were comparable between the two groups, whereas higher levels of cholestatic enzymes (P< 0.001) were reported in the hepatitis G virus/hepatitis C virus-positive patients. A liver biopsy was performed on all 40 patients no later than 6 months before recruitment. The mean histological activity index did not differ between hepatitis G virus-positive and hepatitis G virus-negative patients, whereas specific histological features such as macrovesicular steatosis, portal granulomas, and bile duct damage were more commonly observed among the coinfected patients. The results indicate that coinfection with hepatitis G virus probably does not have a significant effect on hepatitis C virus-induced hepatic damage.

Alfa-interferon in the treatment of essential thrombocythemia: clinical results and evaluation of its biological effects on the hematopoietic neoplastic clone. Italian Cooperative Group on ET.

The efficacy of alfa-interferon (alfa-IFN) in essential thrombocythemia (ET) patients has been reported by several authors. The aim of this study is to assess the magnitude of the effect of alfa-IFN on the neoplastic clone. As of December 1993, 11 ET patients received alfa-IFN at a dose of 3-6 MU/s.c./day for 6 months. Ten of 11 obtained complete hematological remission (CHR) and one achieved partial hematological remission. Megakaryocyte concentration was reduced in six cases. The spleen,which was enlarged in four patients, decreased in size in two patients. Seven of eight patients who were symptomatic at diagnosis obtained resolution of symptoms. In order to obtain indications about the structural modifications induced by alfa-IFN in ET megakaryocytes (Mks), Fourier-transform infra-red microspectroscopy analysis performed on 10 single Mks of each patient, was done in seven of 11 patients; the analysis showed a reduction of A1/A2 ratios (A1 integrated area of the band at 1080 cm(-1) due to the nucleic acids absorption; A2 integrated area of the band at 1540 cm(-1) due to proteic components absorption) in five cases, and in three of these five patients A1/A2 ratios achieved normal values. After alfa-IFN treatment we did not observe any change in the methylation pattern of DNA from the granulocyte fraction. Our results confirm the efficacy of alfa-IFN in ET patients, and the decrease of A1/A2 ratios in several patients is a demonstration of the depth of the effect of alfa-IFN on the neoplastic clone. The results of clonality studies showed the persistence of clonal hematopoiesis. Whether higher alfa-IFN dose and/or more prolonged alfa-IFN therapy may allow a restoration of polyclonal hematopoiesis remains to be determined and should be explored in future clinical trials.

[Multiple osteo-articular involvement due to methicillin-resistant Staphylococcus aureus septicaemia: clinical and therapeutic evaluation] / Localizzazione osteoarticolare multipla in corso di sepsi da Staphylococcus aureus meticillino-resistente: considerazioni clinico-terapeutiche.

Here we report a rare case of septic spondilodiskitis by methicillin-resistant Staphylococcus aureus, complicated by the atypical involvement of two articular sites such as manubrio-clavicular joints and right wrist. The source of the septic process was identified in hand's eczematous lesions and paronychia. A first therapeutical attempt performed by combining teicoplanin with netilmicin or rifampicin was useless. A new course with vancomycin instead of teicoplanin favoured the prompt remission of symptoms. Following 10 weeks of continuous treatment, we observed the complete disappearance of all radiological signs of vertebral damage. Though rarely, polyarthritis may complicate a Staphylococcus aureus bacteraemia. An adequate chemio-antibiotic course may lead to definitive recovery and avoid surgery.

[Topical progesterone as support for the luteal phase in induced cycles]. / Il progesterone "topico" come sostegno della fase luteale in cicli indotti.

UNLABELLED: e efficacy and tolerability of 2.5% natural vaginal progesterone as luteal phase support in pharmacologically induced cycles has been evaluated. MATERIALS AND METHODS: On the basis of the administered therapy, the population studied was subdivided at random into four different groups. Sixty patients came to the Sterility Autonomous Department of the Niguarda Ca' Granda Hospital in Milan from November 1994 to January 1996. Both ultrasonographic and plasmatic hormonal parameters have been evaluated on a monthly basis. RESULTS: The plasma progesterone levels and ultrasonographic endometrial thickness average values resulted more important in groups treated with topical progesterone; in these same groups a greater percentage of pregnancies was observed. CONCLUSIONS: The results obtained demonstrated that the drug studied can be recommended as a valid luteal phase support in pharmacologically induced cycles.

[Cervical factor in sterility: treatment with intravaginal estriol]. / Fattore cervicale di sterilità: trattamento con estriolo intravaginale.

BACKGROUND: The aim of our study was to evaluate the efficacy and tolerability of vaginal estriol in treating the isolated cervical factor. METHODS: Three different groups of patients were selected at random on the basis of the administered therapy (estriol, ethinyl-estradiol, bromhexine associated with gonadotropins). The patients (thirty in all) came to the Autonomous Sterility Department of the Niguarda Ca' Granda Hospital in Milan during the November 1994-January 1996 period. The following parameters were evaluated: cervical score according to Insler, cervical pH; in vivo penetration test (PCT) at third and sixth cycle of treatment; evaluation of the hormonal profile during the ovulatory period of estriol, estradiol, LH and progesterone at the third and sixth cycles of treatment; any possible pregnancy. RESULTS: On the whole, 23 patients out of 30 (76.6%) had a positive in vivo penetration test. Particularly, a more favourable result was observed in the group to which vaginal estriol was administered as it presented, at treatment end, a positive PCT in 90% of cases. Moreover, always in the latter group, a greater percentage of pregnancies (40%) was observed. CONCLUSIONS: The obtained results have demonstrated that the drug we have studied can be recommended as a valid therapy for the treatment of the isolated cervical factor of sterility.

[The imaging diagnosis of Sjögren's syndrome: echography, sialography and scintigraphy compared in the study of the salivary glands]. / Diagnostica per immagini della sindrome di Sjögren: ecografia, scialografia e scintigrafia a confronto nello studio delle ghiandole salivari.

The aim of the present study was to evaluate the sensitivity and specificity of the ultrasonography, in comparison with other methods of investigation (scintigraphy, sialography, and biopsy), in scanning morphostructural changes in the parotid gland in patient with Sjögren's syndrome. During the period June-October 1994, 34 patients (5 males and 29 females, age ranged between 20 and 88 years) with "sicca syndrome" underwent to echography, scintigraphy, sialography and biopsy. The diagnosis was confirmed or excluded using the European Community Epidemiologic Committee criteria for Sjögren's syndrome. Twenty-two patients out of 34 were affected by Sjögren's syndrome, while the others resulted as control subjects. The ultrasonographic investigation has shown 76.19% of sensitivity and 30.43% of specificity. Even if echography is a non-invasive method, which could be used as preliminary approach for studying the diffused involvement of the parotid gland, at the status of the art, it is not completely reliable for the global evaluation of the morphostructural changes in patients with Sjögren's syndrome, in comparison with the other techniques. Because of the double nature of the gland injury, it appears to be essential the diagnostic integration between echography and sialography.

A human minor histocompatibility antigen which appears to segregate with the major histocompatibility complex.

We obtained a cell line (So1) from a patient who rejected a T-depleted allogeneic BMT. Cytotoxic activity by cell-mediated lympholysis was found using So1 as effector and EBV-transformed donor B cells as targets, but no lysis of the patient's pretransplantation cells and of an unrelated HLA-nonidentical subject was observed, suggesting it was related to recognition of a minor transplantation antigen which could have contributed to rejection of the graft. To define the HLA-restricting element(s), cell-mediated lympholysis experiments were performed with several B cell lines as targets. So1 lysed only targets sharing an HLA-B44 antigen with the patient, thus demonstrating that the minor transplantation antigen recognized was restricted by HLA-B44. The absence of lysis against the patient's pretransplantation cells may be related to the absence of the minor antigen, suggesting that the patient's cytotoxic lymphocytes able to recognize a minor transplantation antigen on the donor cells contributed to the rejection of the HLA-identical graft. Mendelian segregation of this minor antigen was found in familial studies. Lysis was observed with cells from members of 2 families who had an association of HLA-B44 antigen in the haplotype and the minor antigen, whereas in 2 other HLA-B44-positive families, no lysis was found, probably because this minor antigen was absent. Furthermore, these family studies: (1) demonstrated that this minor antigen segregates with the MHC, suggesting its localization on chromosome 6; and (2) showed a close relationship between the minor antigen and HLA-B44, strongly suggesting a linkage disequilibrium between the minor antigen and its restriction antigen B44.

Evidence that residual host cells surviving the conditioning regimen to allogeneic bone marrow transplantation inhibit donor hematopoiesis in vitro--the role of TNF-alpha.

Blood cells were obtained from patients selected for allogeneic bone marrow transplantation who had undergone a conditioning regimen (CR) with high-dose chemotherapy and total body irradiation. The majority of residual cells bore CD3 antigen (range: 68-98%), and the CD4/CD8 ratio was normal. The effect of these residual/radioresistant cells on donor bone marrow hematopoiesis was investigated in eleven cases. Growth of donor CFU-GM and BFU-E was inhibited by 22-65% and 29-77%, respectively, when donor marrow was cocultured with residual cells at various ratios. In contrast, blood cells obtained from two patients prior to CR had no inhibitory effect. Supernatants obtained following incubation of residual cells from 9 patients were able to inhibit the growth of CFU-GM and BFU-E from normal unrelated subjects, whereas supernatants obtained before CR and from cultured normal marrow had no inhibitory effect. In addition, in blocking experiments, an anti-TNF-alpha MoAb was able to prevent this inhibition. Thus, TBI might be able to select and/or activate cells responsible for hematopoietic growth inhibition by a mechanism involving, at least in part, TNF-alpha.

Autoreactive HLA-DR-specific autoreactive T-cell clones: possible regulatory function for B lymphocytes and hematopoietic precursors.

The physiological significance of autoreactive T cells derived from normal individuals and activated in the absence of any identifiable foreign antigen by class II MHC-syngeneic molecules remains unexplained. Here we report that autoreactive T-cell clones (Tilkin et al. 1987) proliferate and are able to kill autologous or syngeneic EBV-cell lines but not autologous or syngeneic HLA-Class II-positive PHA-activated T-cell blasts. Furthermore, they are able to efficiently inhibit in vitro the differentiation of CFU-GM and BFU-E colonies, in agreement with the well-known observation that hematopoietic precursors express HLA-DR molecules (Cannistra et al. 1986). The reasons why the autoreactive clones do not recognize T-cell blasts, as well as their possible implications in regulatory mechanisms involving HLA-class II molecules are discussed.

Central nervous system relapses after bone marrow transplantation for acute lymphoblastic leukemia in remission.

This study defines the risk of central nervous system (CNS) relapse in patients undergoing bone marrow transplantation (BMT) for acute lymphoblastic leukemia (ALL) in remission, with no posttransplant prophylactic CNS therapy. Ninety-two consecutive patients in complete remission received BMT for ALL (n = 82) or high-grade non-Hodgkin's lymphoma with poor prognostic factors at diagnosis (n = 10). Sixty-six patients received allogeneic BMT (Allo-BMT) and 26 patients, without an identical sibling, underwent autologous BMT (Auto-BMT). Fifteen patients had CNS involvement at diagnosis and underwent BMT in first remission. Eight patients experienced CNS relapse after BMT, corresponding to a probability of 11% at 3 years. Apart from a history of prior CNS involvement, no patient characteristic evaluated statistically influenced CNS relapse after BMT. The probability of CNS relapse was 5.5% for the 70 patients without history of CNS involvement and 27.5% for the 22 patients with prior CNS involvement. However, subgroup analysis showed that the increased risk of CNS relapse is mainly observed in Auto-BMT patients with history of prior CNS involvement, particularly in patients undergoing BMT in first remission (three of five Auto-BMT versus one of ten Allo-BMT). Taking into account the multiple factors which influence the occurrence and the treatment of CNS leukemia, the results on this retrospective study suggests that (1) for patients without CNS involvement at diagnosis and for whom BMT is performed in first remission, cranial irradiation before BMT and posttransplant prophylactic CNS therapy can be omitted because of the low probability of CNS relapse after BMT (3.4%), when total-body irradiation (TBI) is included in the conditioning regimen; and (2) the difference observed between Allo-BMT and Auto-BMT patients with previous CNS involvement and undergoing BMT in first remission could indicate that graft-versus-host leukemia acts even in the CNS in Allo-BMT patients.

In vitro inhibition of normal human hematopoiesis by marrow CD3+, CD8+, HLA-DR+, HNK1+ lymphocytes.

We previously demonstrated that after allogeneic bone marrow transplantation (BMT) a subset of CD8, HNK1, and DR-positive T lymphocytes are able to inhibit CFU-GM and BFU-E growth with an HLA-DR restriction. In this study we investigated whether these cells, present in normal marrow in low concentration (less than 1%), play the same role. HNK1-positive sorted marrow cells forming rosettes (E+C) were able to inhibit BFU-E and CFU-GM growth when added back to the marrow E-C at a ratio of 1:10 (HNK1+ E+C/E-C) in a range from 40% to 60%. This inhibitory effect was also detected for a cellular ratio of 1:100, which is the normal marrow value for this subset of T cell. HNK1+ DR+-sorted E+C after double-immunofluorescent labeling also showed the same inhibitory activity as the HNK1+ E+C, whereas the negative fraction including all the other E+C had no detectable inhibitory activity. CD3 and CD8 antigens were also present on the membrane of these cells, as demonstrated in two cases by double-immunofluorescent labeling performed with anti-CD3 or anti-CD8 monoclonal antibodies (MoAbs) and HNK1 MoAb, respectively, and subsequent cell sorting. Blocking experiments, performed by adding in culture anti-CD4 and anti-CD8 MoAbs to HNK1+ T cells showed that only the last MoAb was able to prevent inhibition of hematopoietic colony growth. These results confirmed that one subset of CD3+, CD8+, HNK1+, and DR+ T cells was responsible for in vitro inhibition of normal hematopoiesis. In addition, this inhibition was genetically restricted to HLA-class II antigens, since in three co-culture experiments with unrelated bone marrow cells inhibition occurred only when cells with one haplo-identical HLA-DR antigen was added back to the culture. Indeed, this effect was really HLA-DR restricted, since in blocking experiments with different anti-HLA class II MoAbs (anti-DR, anti-DP, and anti-DQ MoAbs) only an anti-HLA-DR MoAb was able to prevent the colony growth inhibition by CD3+ HNK1+, or CD8+ HNK1+ E+C. In conclusion, the CD3+, HNK1+, CD8+, DR+ cells may be the T-cell subset able to inhibit normal hematopoiesis with an HLA-DR restriction.