Phenotypical heterogeneity of CD4+CD8+ double-positive chronic T lymphoid leukemia

Abstract

Chronic T lymphoid leukemias are defined as leukemias of post-thymic T cells. The CD4 ؉ CD8 ؉ double-positive (DP) phenotype is seen in a few cases. Since DP generally occurs in thymic T cells, whether the DP T leukemia cells represent thymic or peripheral T cells has been a matter of controversy. To address this issue, we studied phenotypical features in eight cases of DP T cell leukemia. Thymic DP T cells and peripheral CD8 ؉ T cells have CD8 of ␣␤ subunit, while CD8␣␣ is induced in CD4 ؉ T cells on activation with IL-4. We found that two patients with DP T large granular lymphocyte leukemia (LGLL) showed dim expression of CD8␣␣, identical to the phenotype on IL-4-activated DP-T cells. The leukemic cells of these patients expressed IL-4 mRNA and produced high levels of IL-4. These findings suggest that they may be derived from peripheral CD4 ؉ T cells. Three patients with adult T cell leukemia/lymphoma (ATLL) showed CD8␣␣, suggestive of an activated peripheral T cell origin. One case expressed CD8␣␣ dim and IL-4 mRNA, while the other two cases expressed no IL-4 mRNA and showed CD8␣␣ bright phenotype, features not found in normal T cell populations. Three patients with T-prolymphocytic leukemia (T-PLL) expressed CD8␣␤. The DP phenotype is relatively common in T-PLL, and CD4 + CD8␣␤ + is characteristic of thymic T cells. The DP T-PLL cells did not express TdT,CD1 or recombination activating gene-1 (RAG-1), which is down-regulated at the late stage of thymic T cell development. On the basis of these findings, we propose a late thymic origin for DP T-PLL. The phenotype of DP T cells differed for each entity and appeared to correlate with minor normal DP T cell population.

CD8+ T cells that express CD4 on their surface (CD4dimCD8bright T cells) recognize an antigen-specific target, are detected in vivo, and can be productively infected by T-tropic HIV

“…Demonstration of in vivo infection of these cells highlights the role that they may play in HIV-mediated dysregulation in the CD8 ϩ T-cell compartment. 26 Double-positive (CD4 ϩ CD8 ϩ ) T cells have been reported in a number of clinical conditions such as HTLV-1 infection, 29 chronic T-lymphoid leukemia, 35 Sjögren syndrome, 36 myasthenia gravis, [17][18][19]37 multiple sclerosis, 38 idiopathic thrombocytopenic purpura, 39 and Behçet syndrome. 40 These cells may play a role not only in HIV pathogenesis but also may constitute a normal response to CD8 ϩ T-cell activation and, hence, may also play a role in normal T-cell biology.…”

Intestinal double‐positive CD4+CD8+ T cells are highly activated memory cells with an increased capacity to produce cytokines

“…Several investigators have reported the presence of circulating blood DP T cells, in both healthy [13,14] and diseased individuals [15][16][17][18][19][20][21][22]. Existence of this unconventional and rare lymphocyte population in peripheral blood has been hypothesized to result from premature release of immature CD4 + CD8 + T cells from the thymus to the periphery, where their maturation into functionally competent SP cell continues [23].…”

TCL‐1, MTCP‐1 and TML‐1 gene expression profile in non‐leukemic clonal proliferations associated with ataxia‐telangiectasia

“…32 ATM mutations cDNA or DNA samples were screened using PTT or SSCP followed by DNA sequencing to identify the mutations. Germline mutations in the A-T gene were found in all A-T patients (Table III).…”