Cytofluorometric Identification of Two Populations of Double Positive (CD4+,CD8+) T Lymphocytes in Human Peripheral Blood

Ortolani, Claudio; Forti, Elisa; Radin, Elizabeth; Cibin, R.; Cossarizza, Andrea

doi:10.1006/bbrc.1993.1260

Cited by 108 publications

(111 citation statements)

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“…23,24 Their frequency is considerably increased in some autoimmune [25][26][27][28] and infectious diseases. 29,30 DP T cells seem in fact to represent diverse subpopulations. At least three subsets of DP T cells can be distinguished on the basis of their level of CD4 and CD8 expression and by the expression of CD8 aa homodimer or ab heterodimer.…”

Section: Discussionmentioning

confidence: 99%

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

Desfrançois

Derré

Corvaisier

et al. 2009

Intl Journal of Cancer

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Breast cancer remains a leading cause of cancer-related death within the female population. Immunotherapy is expected to provide additional therapeutic benefits but has met so far limited success. This may be due in part to the poor understanding of immune responses to breast cancer. Although CD4 1 and CD8 1 T lymphocytes infiltrate these tumors, the phenotype and functions of these cells remain ill defined. This study was designed to investigate further about these questions, taking advantage of multiparameter flow cytometry on lymphocytes derived from peripheral blood, solid tumors, metastatic lymph nodes and pleural effusions samples of patients with breast cancer. Results showed that, in addition to conventional CD4 1 and CD8 1 ab T cells, individual tumors and most pleural effusions contained significant fractions of unconventional double positive (DP) CD4 1 CD8 1 ab T cells. These DP T cells displayed the phenotype and cytotoxic potential of effector/memory activated CD8 1 T cells but differed essentially from these cells by a high production of IL-5 and IL-13. The increased frequency of DP T cells in advanced breast cancer and their high lytic potential and original cytokine profile suggest that this T-cell subset may play a specific role in the regulation of immune responses to human breast cancer. ' 2009 UICC

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Section: Discussionmentioning

confidence: 99%

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

Desfrançois

Derré

Corvaisier

et al. 2009

Intl Journal of Cancer

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“…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].…”

Section: Introductionmentioning

confidence: 99%

“…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]. However, in HIV and Epstein-Barr virus infections, the percentage of DP T cells can increase to 20% of circulating lymphocytes, suggesting they are effector cells responding to infection [14,15]. In humans and animals DP T cells have also been shown to have antiviral activity, further suggesting they are indeed antigen-specific effector cells rather than immature cells from the thymus [2, 4,24].…”

Section: Introductionmentioning

confidence: 99%

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

2006

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Peripheral blood and intestinal CD4 + CD8 + double-positive (DP) T cells have been described in several species including humans, but their function and immunophenotypic characteristics are still not clearly understood. Here we demonstrate that DP T cells are abundant in the intestinal lamina propria of normal rhesus macaques (Macaca mulatta). Moreover, DP T cells have a memory phenotype and are capable of producing different and/or higher levels of cytokines and chemokines in response to mitogen stimulation compared to CD4 + single-positive T cells. Intestinal DP T cells are also highly activated and have higher expression of CCR5, which makes them preferred targets for simian immunodeficiency virus/HIV infection. Increased levels of CD69, CD25 and HLA-DR, and lower CD62L expression were found on intestinal DP T cells populations compared to CD4 + single-positive T cells. Collectively, these findings demonstrate that intestinal and peripheral blood DP T cells are effector cells and may be important in regulating immune responses, which distinguishes them from the immature DP cells found in the thymus. Finally, these intestinal DP T cells may be important target cells for HIV infection and replication due to their activation, memory phenotype and high expression of CCR5. IntroductionCD4 + CD8 + double positive (DP) T cells in the intestine have been shown to be a major early target in primary simian immunodeficiency virus (SIV) infection [1]. Rapid depletion of intestinal DP cells occurs faster and more profoundly than that of intestinal CD4 + singlepositive (SP) cells which we have previously correlated with increased levels of CCR5 expression on the former [1]. Although DP T cells have been described in the blood and intestine of humans, nonhuman primates, swine and rodents [2][3][4][5][6][7][8][9][10][11][12], little is known regarding their function or immunophenotypic (naive versus memory status etc.) characteristics. DP T cells are perhaps best known in the thymus, where they are T cell precursors in early states of T cell maturation. However, DP T cells in the peripheral blood have been shown to differ from those in the thymus [2].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]. However, in HIV and Epstein-Barr virus infections, the percentage of DP T cells can increase to 20% of circulating lymphocytes, suggesting they are effector cells responding to infection [14,15]. In humans and animals DP T cells have also been shown to have antiviral activity, further suggesting they are indeed antigen-specific effector cells rather than immature cells from the thymus [2, 4,24]. The intestine is the major target organ of HIV...

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“…2 Transient or persistent increases in DP-T cell numbers were recognized in patients with several diseases including viral infections and collagen diseases, and in apparently normal individuals. [3][4][5][6] DP T cell lymphocytosis appears to involve an increase in the number of activated peripheral T cells.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 1998

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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.

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Cytofluorometric Identification of Two Populations of Double Positive (CD4+,CD8+) T Lymphocytes in Human Peripheral Blood

Cited by 108 publications

References 0 publications

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

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

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

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Cytofluorometric Identification of Two Populations of Double Positive (CD4+,CD8+) T Lymphocytes in Human Peripheral Blood

Cited by 108 publications

References 0 publications

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

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

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

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