Antigens, Surface ; analysis ; Antiretroviral Therapy, Highly Active ; CD28 Antigens ; analysis ; CD56 Antigen ; analysis ; HIV Infections ; drug therapy ; immunology ; Humans ; Killer Cells, Natural ; immunology ; Lectins, C-Type ; analysis ; NK Cell Lectin-Like Receptor Subfamily B ; NK Cell Lectin-Like Receptor Subfamily D ; analysis ; Receptors, Immunologic ; analysis ; Receptors, KIR

<b>OBJECTIVEb>To investigate the expression and possible role of C-type lectin-like natural killer cell receptors, including CD94 and NKG2s, in extranodal NK/T-cell lymphoma, nasal type (EN-NK/T-NT).

<b>METHODSb>Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of CD94 and NKG2s in tissue sections of 21 cases of EN-NK/T-NT(confirmed by histology, immunohistochemistry, in-situ hybridization for Epstein-Barr virus(EBV) and PCR for T-cell receptor genes), eight midline B cell lymphomas (BCL), 10 peripheral T cell lymphoma of lymph nodes (PTCL), five spleens, five thymuses and five chronic nasopharyngitis.

<b>RESULTSb>All 21 cases of EN-NK/T-NT showed typical histological features, with expression of CD3epsilon, CD56, cytotoxic granules and positivity of EBV in 20 cases. The RT-PCR results showed a high level expression of CD94 (85.7%) and NKG2 members (95.2% totally, with NKG2A/2B in 85.7%, NKG2D in 61.9%, NKG2F in 14.3%, NKG2C/2E in 4.8%, respectively and sequentially) in EN-NK/T-NT. But in the controls, none of the receptors were detected in TCL (0%) and BCL (0%), while only a few cases of lymphoid tissues expressed one or two of these receptors (two spleens and two chronic nasopharyngitis mucosa for CD94, one spleen for NKG2A/2B and one thymus for NKG2D). The differences of CD94 and NKG2 expression between EN-NK/T-NT and BCL or TCL were statistically significant (P<0.01). Co-expression of CD94 and NKG2 was found in 17 out of 21 EN-NK/T-NT cases (81.0%).

<b>CONCLUSIONSb>The specific and sequential expression nature of CD94 and NKG2 in EN-NK/T-NT, mimics the developmental expression model in their normal counterparts, and suggests that the tumor cells of most cases are being activated and keeping in a stage as the functional NK cells. Detection of these molecules may provide a useful tool to confirm the diagnosis of NK cell lymphoma.

Adolescent ; Adult ; Aged ; Diagnosis, Differential ; Epstein-Barr Virus Infections ; virology ; Female ; Follow-Up Studies ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Lymphoma, B-Cell ; metabolism ; pathology ; Lymphoma, Extranodal NK-T-Cell ; diagnosis ; metabolism ; pathology ; virology ; Lymphoma, T-Cell, Peripheral ; metabolism ; pathology ; Male ; Middle Aged ; NK Cell Lectin-Like Receptor Subfamily C ; metabolism ; NK Cell Lectin-Like Receptor Subfamily D ; metabolism ; Nose Neoplasms ; diagnosis ; metabolism ; pathology ; virology ; Survival Rate ; Young Adult

<b>OBJECTIVEb>To observe the changes in hepatitis B virus (HBV)-specific and non-specific cellular immunity that accompany viral load decline during adefovir dipivoxil (ADV) treatment in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, and to explore the antiviral immunity mechanism underlying the treatment response.

<b>METHODSb>Serial analysis of cellular immunological parameters was performed in HBeAg-positive patients (n = 20) throughout the 48-week course of ADV therapy (10 mg/d). HBV-specific T cell reactivity to HBV core antigen (HBcAg) was assessed by enzyme-linked immunosorbent spot assay and cell proliferation assay at pre-treatment (baseline) and post-treatment weeks 4, 12, 24, 36, and 48. Percentage of regulatory T cells (Tregs), as well as activated peripheral natural killer (NK) cells (expressing the NKG2D receptor), was measured by flow cytometry. Comparisons of means were performed by the two-tailed t-test or the Mann-Whitney rank sum test.

<b>RESULTSb>After 48 weeks of ADV therapy, HBeAg loss was observed in six of the 20 (30%) patients and 14 patients remained HBeAg-positive. In the patients with HBeAg loss, the viral load reduction was accompanied by a significantly enhanced response rate of HBV-specific interferon (IFN)-gamma-producing CD4+ T cells [measured as (spot forming cells/peripheral blood mononuclear cells); baseline: (661.25+/-281.97) *10(-6) vs. week 48: (280.75+/-104.33) *10(-6), P = 0.045]. In contrast, patients without HBeAg loss showed no significant differences in T cell response rates. The patient groups with and without HBeAg loss showed similar proportions of peripheral blood Tregs during the treatment course, which included a trend of gradual decrease from baseline to week 4 with steady levels thereafter. In addition, both groups showed a similar increase in NKG2D expression that began at week 12 and peaked at week 48.

<b>CONCLUSIONb>HBV-specific T cell reactivity temporally increases in some ADV-treated chronic hepatitis B patients, and this trend is strongly associated with HBeAg loss. Furthermore, recovery of HBV-specific T cell reactivity promotes viral clearance and HBeAg seroconversion.

Adult ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; drug therapy ; immunology ; Humans ; Killer Cells, Natural ; immunology ; Male ; NK Cell Lectin-Like Receptor Subfamily K ; metabolism ; T-Lymphocytes, Regulatory ; immunology ; Viral Load ; Young Adult