Immunopathology of cutaneous T-cell lymphomas.

In this study the authors attempted to establish immunopathologic criteria for the distinction of various T-cell lymphomas affecting the skin. We studied skin specimens from 27 patients with mycosis fungoides (MF) (n = 12), the Sézary syndrome (SS) (n = 6), adult T-cell leukemia (ATL) (n = 4), and nonepidermotropic T-cell lymphoma of large cell (n = 4) and lymphoblastic (n = 1) types. Identification of tumor cells in mixed cell populations and detection of weak expression of surface antigens by tumor cells was facilitated by immunoelectron microscopy. The mature helper T-cell phenotype (T11+ T3+ T4+) was found in 14 of 18 cases of MF/SS. One case of MF had a cytotoxic/suppressor (T4- T8+ 3A1+) phenotype; one with frequent blastic cells showed only weak expression of T4 antigen; 2 cases of SS were T11-. Tumor cells infiltrating the skin expressed 3Al antigen in 44% and cellular activation antigens Ia and/or Tac in 78% of patients with MF/SS. No consistent phenotypic differences were found between ATL cells from ATLV (HTLV) antibody-positive patients and tumor cells of patients with MF/SS who lacked this antibody. In contrast, a group of nonepidermotropic T-cell lymphomas showed phenotypic differences from MF/SS and ATL in all but 1 case. These cases were distinguished by the frequent absence of T3, T4, and Leu 1 antigens in 3 large-cell lymphomas; frequent expression of Ki-1 antigen, a Hodgkin's disease-associated antigen, in 2 cases with RS-like cells; and an immature thymocyte phenotype in lymphoblastic lymphoma. These findings demonstrate that tumor-cell phenotypes can be useful in distinguishing different histologic types of cutaneous T-cell lymphoma.     

Peripheral T-cell lymphoma with helper T-cell phenotype (Leu 3a+ Leu 8-)

Eleven cases of Leu 3a+ Leu 8- peripheral T-cell lymphoma (PTCL), excluding adult T-cell leukemia/lymphoma, were studied by immunostaining with monoclonal antibodies and enzyme histochemistry in order to clarify the histogenesis of PTCL. Seven of the eleven cases had varying degrees of polyclonal hypergammaglobulinemia. All cases were histologically characterized by neoplastic proliferation of clear cells and some cases showed a histologic background similar to IBL or AILD lesions with proliferation of immunoblasts or plasmacytoid cells and vascular proliferation. Immunohistologic analysis of PLP-fixed frozen tissues revealed that neoplastic clear cells expressed a Leu 3a+ Leu 8- phenotype (helper T-cell subset). The distribution of Leu 3a+ Leu 8- neoplastic cells corresponded closely to that of DRC-1+ cells, which are localized in the lymphatic follicles, but hardly at all with that of beta-glucuronidase+ vessels, termed PCV or HEV, which are usually present in T-cell areas. One case only progressed from Leu 3a+ Leu 8- IBL-like T-cell lymphoma (IBL-T), with proliferation of immunoblasts or plasmacytoid cells and vascular proliferation, to diffuse lymphoma of the large cell type showing none of these lesions. From these observations it is suggested that IBL-T might progress to T-cell-type monomorphous diffuse lymphoma.     

Double immunoenzymatic detection of surface phenotype of proliferating lymphocytes in situ with monoclonal antibodies against DNA polymerase alpha and lymphocyte membrane antigens

To detect the proliferating cells in situ, a monoclonal antibody against human DNA polymerase alpha (pol alpha) was employed because this enzyme is known to be present in the nucleus of the cells in G1, S, and G2 phases. In addition, the surface phenotype of pol alpha-positive proliferating lymphocytes in diseased lymph nodes was determined by double staining consisting of immunoperoxidase and immunoalkaline phosphatase methods with various monoclonal antibodies against lymphocyte membrane antigens. In the paracortical area of lymph nodes with reactive changes, proliferating cells were 17% or less, and most of them were helper T-cells, although suppressor T-cells and B-cells also proliferate to a certain extent. In contrast, the proliferating cell population in malignant lymphomas was generally more than 40%, and it showed a single surface phenotype, indicating monoclonal proliferation. In addition, an unusual T-cell antigen phenotype of proliferating cells was observed in some cases of peripheral T-cell lymphomas. Thus, this double staining provided the authors with valuable information regarding the proportion, localization, and surface phenotype of proliferating cells, which should be useful for diagnosis of the diseases of lymphoid system.     

Analysis of T-cell subpopulations in T-cell non-Hodgkin's lymphoma of angioimmunoblastic lymphadenopathy with dysproteinemia type by single target gene amplification of T cell receptor- beta gene rearrangements

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is defined in the current lymphoma classifications as a T-cell non-Hodgkin's lymphoma. However, in approximately one third of the cases of this lymphoproliferative disease rearrangements of T-cell receptor (TCR) genes indicating clonal expansion of T cells are not detectable. It is currently believed that these cases may represent early stages of a lymphoma with a minor oligoclonal T-cell population. In the present study, 18 lymph nodes with the characteristic histology of AILD were investigated for clonal T-cell receptor gene rearrangements by analysis of DNA extracted from whole tissue sections. Dominant T-cell clones were detected in 12 of these cases. Single CD4(+) and CD8(+) T cells and proliferating Ki67(+) cells of seven cases were micromanipulated from frozen tissue sections. TCRbeta gene rearrangements were amplified from these cells by polymerase chain reaction and sequenced. In all informative cases, the clonal gene rearrangements were only detected among CD4(+), and not among CD8(+) T cells, indicating that the tumor clones in AILD usually derive from CD4(+) T cells. Minor clonal T-cell populations in those cases in which no clone was found by whole-tissue DNA analysis were not detectable even at single cell resolution. T-cell clones in 4 of 10 cases were found to express similar TCRbeta chains, indicating a potential role of (super) antigen triggering in at least some cases of AILD.     

Various membrane proteins of Francisella tularensis induce interferon-gamma production in both CD4+ and CD8+ T cells of primed humans.

Tularaemia is an intracellular infection, which is controlled by the host as a result of an immunospecific T-cell response. A crucial product of the responding T cells is interferon-gamma (IFN-gamma), which acts by enhancing the microbicidal activity of macrophages. T cells of tularaemia-vaccinated individuals respond in vitro to a multitude of protein antigens of the vaccine strain Francisella tularensis LVS. In the present study, the responses to four of these antigens were shown to be confined mostly to the CD45RO+ memory T-cell subset. To characterize further the phenotype of the responding cells, purified CD4+ and CD8+ T cells were stimulated with the antigens. CD4+ T cells, but not CD8+ T cells, proliferated and produced IFN-gamma. However, when CD8+ T cells were isolated from bulk cultures of lymphocytes, which had been stimulated with antigen for 3 days, they responded to an extent similar to that of CD4+ T cells. Purified CD8+ T cells also responded when they were supplemented with interleukin-2 (IL-2). There was a direct quantitative correlation between the proliferative response of CD4+ and CD8+ T cells and their production of IFN-gamma. IL-2 was produced in the cultures, the amounts being higher in the cultures of CD4+ than in those of CD8+ cells. IL-4 was not detected in the culture medium of any of the T-cell subsets. Seventeen human alpha beta + CD4+ CD8- CD3+ T-cell clones, specific to antigens of F. tularensis, were raised. When proliferating, these clones did invariably produce IL-2 and IFN-gamma but no IL-4. In conclusion, both CD4+ and CD8+ T cells of tularaemia-vaccinated individuals respond with proliferation to various protein antigens of F. tularensis, and the proliferative response is strictly associated with IFN-gamma production. The CD8+ T-cell response seems to depend on cytokines supplied by proliferating CD4+ T cells.     

PERIPHERAL T-CELL LYMPHOMA WITH HELPER T-CELL PHENOTYPE (LEU 3a+ LEU 8−)

Eleven cases of Leu 3a⁺ Leu 8⁻ peripheral T-cell lymphoma (PTCL), excluding adult T-cell leukemia/lymphoma, were studied by Immunostalning with monoclonal antibodies and enzyme histochemistry in order to clarify the histogenesis of PTCL. Seven of the eleven cases had varying degrees of polyclonal hypergammaglobulinemia. All cases were histologically characterized by neoplastic proliferation of clear cells and some cases showed a histologic background similar to IBL or AILD lesions with proliferation of 1m-munoblasts or plasmacytoid cells and vascular proliferation. Immunohis-tologic analysis of PLP-flxed frozen tissues revealed that neoplastic clear cells expressed a Leu 3a⁺ Leu 8⁻ phenotype (helper T-cell subset). The distribution of Leu 3a⁺ Leu 8'neoplastic cells corresponded closely to that of DRC-1⁺ cells, which are localized in the lymphatic follicles, but hardly at all with that of β-glucuronidase⁺ vessels, termed PCV or HEV, which are usually present in T-cell areas. One case only progressed from Leu 3a⁺ Leu 8⁻ IBL-like T-cell lymphoma (IBL-T), with proliferation of immunoblasts or plasmacytoid cells and vascular proliferation, to diffuse lymphoma of the large cell type showing none of these lesions. From these observations it is suggested that IBL-T might progress to T-cell-type monomorphous diffuse lymphoma.     

Peripheral T-cell lymphoma of AILD (angioimmunoblastic lymphadenopathy with dysproteinemia) type involving gastrointestinal tract. A morphologic, phenotypic and genotypic study.

A case of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) which showed widespread involvement of the gastrointestinal tract is reported. A lymph node biopsy specimen showed the characteristic histological features of AILD. During the progression of the illness, lymphomatous lesions developed in the gastrointestinal tract, complicated by cytomegalovirus infection. A double immunoenzymatic study using a combination of Ki-67 antibody and antibodies against surface antigens demonstrated that CD3+, CD4+, and/or T-cell receptor (TCR) beta+ cells were predominant (67-68%) among the population of proliferating Ki-67% cells, rather than CD8+ or CD22+ cells. Clonal rearrangement of the TCR beta chain gene was also detected. These findings provide further evidence for the neoplastic nature of lesions of this type, and the diagnosis of peripheral T-cell lymphoma.     

The usefulness of flow cytometric CD10 detection in the differential diagnosis of peripheral T-cell lymphomas

We studied the histologic and multiparameter flow cytometry (MFC) features of 12 cases of angioimmunoblastic T-cell lymphoma (AITL), 13 of mature T-cell lymphoma, and 25 control cases of reactive lymphoid hyperplasia to evaluate the role of CD10 in the differential diagnosis of peripheral T-cell lymphomas (PTCLs). A characteristic immunophenotypic profile (CD2+/CD4+) with recurrent phenotypic aberrancies (eg, CD3 and CD7 loss) was identified in most AITL cases; MFC documented CD10 coexpression on T cells in 10 (83%). Mature T-cell lymphoma showed a more heterogeneous altered immunophenotypic pattern, and 2 cases of PTCL, unspecified, had clear evidence of aberrant CD10 expression on T cells. A small physiologic CD3+/CD4+/CD10+ T-cell population was detected by MFC in all control cases tested (range, 0.28%-4.71%), suggesting that a normal subset of peripheral CD10+ T cells exists. CD10 was a highly sensitive but incompletely specific phenotypic marker for diagnosing AITL; the differential diagnosis of PTCL, unspecified, must be related with traditional histologic features. A small number of CD10+ T cells in reactive lymph nodes suggests that this subpopulation may be the normal counterpart of neoplastic T cells in AITL. The biologic role of CD10+ T cells should be studied further.     

Immunohistochemical analysis of peripheral T-cell lymphoma in Japanese patients

The authors immunohistochemically analyzed the phenotype of 40 cases of peripheral T-cell lymphoma, including 12 adult T-cell leukemia/lymphoma (ATL) cases. Molecular genetic analysis of the T-cell receptor beta-chain and immunoglobulin heavy chain genes were also applied to cases of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-like lymphoma and so-called Lennert's lymphoma. Twenty non-ATL lymphomas expressed a helper/inducer phenotype, whereas only one extranodal case expressed a suppressor/cytotoxic phenotype. Three cases had a CD4-CD8- phenotype, and two cases a CD4+CD8+phenotype. No specific relationship between morphologic characteristics (LSG classification) and phenotype was found among non-ATL lymphomas. Six of eight AILD-like lymphomas had a helper/inducer phenotype. Monoclonality of neoplastic T-cells was demonstrated in six of the seven cases of AILD-like lymphoma by molecular genetic analysis. Two cases of Lennert's lymphoma also showed a helper/inducer phenotype and rearrangement of the T-cell receptor beta-chain gene. Serologically defined ATL cases had a helper/inducer phenotype except in one case that expressed both CD4 and CD8. None of the ATL cases had the CD7 antigen in this study using WT 1 as a CD7 antibody, which is in contrast with the non-ATL lymphomas in which 13 of 25 cases expressed CD7. CD25, strongly detectable in all ATL cases, was negative or weakly expressed in non-ATL lymphomas. These facts suggest that non-ATL and ATL are in the different biologic state, probably resulting from the integration of human T-cell leukemia virus type I (HTLV-I), although both are derived from helper/inducer T-cells.     

Expansion of mycobacterium-reactive gamma delta T cells by a subset of memory helper T cells.

Human gamma delta T cells expressing the V gamma 9/V delta 2 T-cell receptor have been previously found to proliferate in response to certain microorganisms and to expand throughout life, presumably because of extrathymic activation by foreign antigens. In vitro expansion of V gamma 9/V delta 2 cells by mycobacteria has been previously shown to be dependent on accessory cells. In order to gain an insight into the mechanisms involved in the expansion of these cells, we have undertaken to identify the peripheral blood subset of cells on which proliferation of V gamma 9/V delta 2 cells in response to mycobacteria is dependent. Contrary to their role in antigen presentation to alpha beta T cells, professional antigen-presenting cells, such as monocytes, B cells, and dendritic cells, were unable to provide the cellular support for the expansion of V gamma 9/V delta 2 cells. Selective depletion of T-cell subsets, as well as the use of highly purified T-cell populations, indicated that the only subset of peripheral blood cells that could expand V gamma 9/V delta 2 cells were CD4+ CD45RO+ CD7- alpha beta T cells. These cells underwent distinct intracellular signaling events after stimulation with the mycobacterial antigen. Expansion of V gamma 9/V delta 2 cells by alpha beta T cells was dependent on cell-cell contact. This is the first evidence that a small subset of the memory helper T-cell population is exclusively responsible for the peripheral expansion of V gamma 9/V delta 2 cells. These data illustrate a unique aspect of antigen recognition by gamma delta T cells and provide new means to study their immune defense role.     

Stepwise development of chromosomal abnormalities in angioimmunoblastic lymphadenopathy

Cytogenetic studies of lymphoproliferative diseases, such as angioimmunoblastic lymphadenopathy (AILD), may provide a clue to the understanding of tumor development. Angioimmunoblastic lymphadenopathy may evolve from a nonmalignant lymphoproliferation into a peripheral T-cell lymphoma or even into a high-grade B-cell lymphoma and thus offers the chance to observe cytogenetic changes during lymphoma development. We report the cytogenetic findings in 24 cases of AILD. They are discussed together with 18 previously published cases from the same series. A striking feature was that unrelated chromosome abnormalities, both clonal and nonclonal, were frequently observed. Eighteen of 25 cases with aberrant clones show trisomy 3 (a characteristic chromosome abnormality in peripheral T-cell lymphoma), trisomy 5, or both. This finding provides cytogenetic evidence that these cases are definitely peripheral T-cell lymphomas. From the results of the 42 cases, hypotheses of stepwise evolution of the chromosome abnormalities in AILD are deduced: the first step is the appearance of chromosome abnormalities in different cells because of a genetic instability. At this time, clonal proliferation of T cells was already demonstrated by the rearrangement of T-cell receptor genes. As a second step, chromosomally aberrant clones become established. A cytogenetically detectable monoclonal proliferation represents the third step.     

Peripheral T-cell Lymphoma of AILD (Angioimmunoblastic Lymphadenopathy with Dysproteinemia) Type Involving Gastrointestinal Tract

A case of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) which showed widespread involvement of the gastrointestinal tract is reported. A lymph node biopsy specimen showed the characteristic histological features of AILD. During the progression of the illness, lymphomatous lesions developed in the gastrointestinal tract, complicated by cytomegalovirus infection. A double immunoenzymatic study using a combination of Ki 67 antibody and antibodies against surface antigens demonstrated that CD3⁺, CD4., and/or T cell receptor (TCR) beta⁺ cells were predominant (67–68%) among the population of proliferating Ki 67⁺ cells, rather than CD8⁺ or CD22⁺ cells. Clonal rearrangement of the TCR beta chain gene was also detected. These findings provide further evidence for the neoplastic nature of lesions of this type, and the diagnosis of peripheral T cell lymphoma.     

Intracellular expression of interleukin-4 and interferon-gamma by a Mycobacterium tuberculosis antigen-stimulated CD4+ CD57+ T-cell subpopulation with memory phenotype in tuberculosis patients

In some chronic pathological conditions, antigen persistence activates and expands the CD4+ CD57+ T-cell subset. The host immune response against tuberculosis infection is maintained through the continuous presence of antigen-stimulated effector/memory helper T cells. To determine whether CD4+ CD57+ T cells were also expanded in human tuberculosis, we analysed (by flow cytometry) the phenotype of peripheral blood CD4+ T cells from 30 tuberculosis patients and 30 healthy controls. We observed a significant increase in the CD4+ CD57+ T-cell subset in tuberculosis patients in comparison to healthy controls (P < 0.001). Most CD4+ CD57+ T cells exhibited a CD28- CD45RO+ CD62L- phenotype, which is associated with memory cells. In vitro, a higher number of antigen-stimulated CD4+ CD57+ T cells produced intracellular interferon-gamma and interleukin-4 compared with antigen-stimulated CD4+ CD57- T cells (P < 0.001). These findings suggest that the majority of CD4+ CD57+ T cells correspond to a phenotype of activated memory T cells.     

Immunophenotypic and antigen receptor gene rearrangement analysis in T cell neoplasia.

The author reviews the immunophenotypic profiles displayed by the major clinicopathologic categories of T cell neoplasia, the immunophenotypic criteria useful in the immunodiagnosis of T cell neoplasia, and the contributions made by antigen receptor gene rearrangement analysis to the understanding of T cell neoplasia. Neoplasms belonging to distinct clinicopathologic categories of T cell neoplasia often exhibit characteristic immunophenotypic profiles. Approximately 80% of lymphoblastic lymphomas and 20% of acute lymphoblastic leukemias express phenotypes consistent with prethymic and intrathymic stages of T cell differentiation, including intranuclear terminal deoxynucleotidyl transferase. Cutaneous T cell lymphomas of mycosis fungoides type usually express pan-T cell antigens CD2, CD5, and CD3, often lack the pan-T cell antigen CD7, and usually express the mature, peripheral helper subset phenotype, CD4+ CD8-. Cutaneous T cell lymphomas of nonmycosis fungoides type and peripheral T cell lymphomas often lack one or more pan-T cell antigens and, in addition, occasionally express the anomalous CD4+ CD8+ or CD4- CD8- phenotypes. T gamma-lymphoproliferative disease is divisable into two broad categories: those cases that are CD3 antigen positive and exhibit clonal T cell receptor beta chain (TCR-beta) gene rearrangements and those cases that are CD3 antigen negative and exhibit the TCR-beta gene germline configuration. Human T cell lymphotropic virus-I (HTLV-I) associated Japanese, Carribean, and sporadic adult T cell leukemia/lymphomas usually express pan-T cell antigens, the CD4+ CD8- phenotype, and various T cell-associated activation antigens, including the interleukin-2 receptor (CD25). Immunophenotypic criteria useful in the immunodiagnosis of T cell neoplasia include, in increasing order of utility, T cell predominance, T cell subset antigen restriction, anomalous T cell subset antigen expression, and deletion of one or more pan-T cell antigens. Only in exceptional circumstances do normal, non-neoplastic T cell populations express the CD4- CD8- or the CD4+ CD8+ phenotype and/or lack one or more pan-T cell antigens. T cell receptor beta chain gene rearrangement analysis represents an accurate, objective, and sensitive molecular genetic marker of T cell lineage and clonality that allows discrimination among non-T cell, polyclonal T cell and monoclonal T cell populations. Non-T cells exhibit the TCR-beta gene germline configuration.(ABSTRACT TRUNCATED AT 400 WORDS)     

Distribution and heterogeneity of cells detected by HNK-1 monoclonal antibody in blood and tissues in normal, reactive and neoplastic conditions

When studied with double staining techniques HNK-1+ cells include subsets not expressing T cell antigens (A), expressing T8 antigens (B) and expressing T4 antigens (C). Cells with phenotype A are observed as the dominant HNK-1+ population (greater than 50% of all HNK-1+ cells) in the blood from controls and from patients with solid tumours, infectious mononucleosis and sarcoidosis. Cells with phenotype B are always a substantial subset (35% of HNK-1+ cells) in the peripheral blood but in patients with B chronic lymphocytic leukaemia and angioimmunoblastic lymphadenopathy these cells are present in an even higher percentage (greater than 50% of all HNK-1+ cells). This cell subset is the only HNK-1+ population found in the few tumour samples where HNK-1+ cells are identifiable. Apart from these few cases of malignancies, the type A and B subsets are rare in the tissues. In these samples Leu 11+ cells seem to be absent. In contrast, cells with phenotype C are a minor population in the blood but represent most HNK-1+ cells in the germinal centres of lymph nodes and their malignant counterparts in follicular centre cell lymphoma. These HNK-1+, T4+ cells are Leu 11-. These phenotypic characteristics indicate that the most efficient NK cells may represent a circulating and not a tissue seeking population.     

Benign CD10-positive T cells in reactive lymphoid proliferations and B-cell lymphomas.

Recent reports have indicated that the neoplastic T cells of angioimmunoblastic T-cell lymphoma express CD10. It has been suggested that the demonstration of a CD10+ T-cell population may assist in establishing a diagnosis of angioimmunoblastic T-cell lymphoma and in distinguishing angioimmunoblastic T-cell lymphoma from other peripheral T-cell lymphomas. It has been unclear, however, whether this phenotypically unusual T-cell population might be present in other settings as well. In this report, we have retrospectively examined 64 cases of lymph node and solid tissue biopsies for the presence of CD10+ T cells using multicolor flow cytometry. Discrete populations of CD10+ T cells were found in 5 of 28 cases (18%) of reactive lymphoid hyperplasia, 4 of 17 cases (23%) of follicular lymphoma, and 9 of 19 cases (47%) of marginal zone B-cell lymphomas. The CD10+ T cells constituted 1-6% of total cells analyzed and 相似文献   

Differential thymus dependence of rat CD8 isoform expression.

Expression of the rat CD8 molecule was studied using five novel monoclonal antibodies (mAb), four of which are specific for the V-like domain of CD8 alpha, whereas one reacts either with the beta chain or with a determinant only expressed on the CD8 alpha/beta heterodimer. mAb to both chains effectively blocked purified lymph node CD8 T cells in mixed lymphocyte reaction and in cell-mediated cytotoxicity. Flow cytometric analysis showed that CD8 T cells from lymph nodes or spleen of normal rats almost exclusively express the alpha/beta isoform, regardless of the T cell receptor isotype (alpha/beta or gamma/delta). In contrast, natural killer (NK) cells carry only CD8 alpha chains. This CD8 alpha + beta - phenotype was also prominent among CD8 T cells from athymic rats and from intestinal epithelium of normal rats. CD8 alpha homodimers can also be expressed as a result of activation, as shown by analysis of CD4 CD8 double-positive T cells obtained from highly purified lymph node CD4 T cells by in vitrok stimulation. Such CD4+CD8 alpha + beta - cells also represent a major subset among adult intestinal intraepithelial lymphocytes (IEL), suggesting local activation. Taken together, the difference in CD8 isoform expression among T cells from athymic rats, NK cells, and gut IEL versus CD8 T cells from peripheral lymphatic organs of euthymic animals suggests that like in mice, expression of the CD8 heterodimer is more dependent on intrathymic maturation than that of the homodimer. Since the more stringent thymus dependence of CD8 alpha + beta + T cells may be due to a requirement for thymic selection on self major histocompatibility complex class I antigens, the virtually exclusive CD8 alpha + beta + phenotype of peripheral rat gamma/delta T cells could mean that antigen recognition by this subset is also restricted by MHC class I molecules.     

Clonal gene rearrangement patterns correlate with immunophenotype and clinical parameters in patients with angioimmunoblastic lymphadenopathy.

T cell receptor beta (TcR beta) chain gene rearrangements have been reported in cases of angioimmunoblastic lymphadenopathy (AILD) and provided evidence for the presence of clonal T cell proliferations in this disorder. Twenty-three cases of AILD and two cases of hyperimmune reaction (HR) were investigated. In the two HR cases, essentially the same histologic pattern was present as in AILD but lymph node follicles were hyperplastic. Both HR cases showed germline configuration for the TcR and immunoglobulin heavy chain (IgH) genes. All other patients diagnosed with AILD had clonal rearrangements for TcR gamma and beta chain genes. In addition, seven out of these cases had clonally rearranged their IgH genes. These two different rearrangement patterns (TcR with or without Ig gene rearrangement) correlated to immunohistochemical and clinical data. Cases with TcR but without Ig gene rearrangements (group I) exclusively showed CD4+ proliferating T cells, whereas those cases with TcR and Ig gene rearrangements had significantly elevated numbers of CD8+ proliferating cells (group II). Group II patients significantly more often presented with hemolytic anemia and went into transient remission spontaneously or under steroid treatment. Group I patients, however, had a higher response to chemotherapy and a longer survival time. These data show that, based on different rearrangement patterns, it is possible to divide AILD into two different groups with distinct immunophenotypic properties and differences in clinical parameters. Immunogenotyping in AILD thus will have prognostic and therapeutic implications.     

Peripheral T-cell lymphomas. Immunophenotype, lymphokine production, and immunologic functional characteristics of the lymph-node malignant T cells.

Immunophenotype and functions of the malignant T cells to secrete various T-cell derived lymphokines and to respond in autologous mixed lymphocyte reaction (AMLR) and allogeneic mixed lymphocyte reaction (MLR) of the six patients with peripheral T-cell lymphomas (PTL) are presented. Three cases showed CD3/TcR alpha beta discordance (1 CD3+/TcR alpha beta-; 2 CD3-/TcR alpha beta+) and one showed absence of both these antigens (CD3-/TcR alpha beta-). In addition, we found that 50% of cases expressed CD25+, CD38+, and CD71+ activation antigens. The CD3/TcR alpha beta discordance and expressions of activation antigen noted in these cases were typical and similar to those reported from elsewhere. These malignant T cells from all cases whether CD25+ or CD25- (resting) expressed elevated interleukin-2 receptors (IL-2R) on stimulation with phytohemagglutinin (PHA) or human recombinant interleukin-2(rIL-2), and secreted elevated IL-2 by PHA, than do T cells from patients with tuberculosis (TB) or normal healthy controls. These malignant T cells also demonstrated elevated AMLR but deficient MLR B cells growth factor (BCGF) (except in one unusual case) secretion was increased, whereas B-cell differentiation factor (BCDF) secretion decreased. These results suggest that malignant T cells from lymph nodes of patients with PTL have uniform multiple immunologic defects in IL-2, BCGF, and BCDF lymphokine secretion and respond in AMLR and MLR, which do not correlate with immunophenotype or histologic types. These functions differentiate them from lymph-node T cells of patients with TB or blood T cells of normal healthy controls.