CD7
T-cell antigen CD7 precursor (GP40) (T-cell leukemia antigen) (T-cell surface antigen Leu-9) (TP41) (CD7 antigen)
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CD7 and CD28 are T cell Ig superfamily molecules that share common signaling mechanisms. To determine roles CD7 and CD28 might play in peripheral lymphocyte development and function, we have generated CD7/CD28-double-deficient mice. CD7- and CD28-single-deficient and CD7/CD28-double-deficient mice had normal levels of CD4 and CD8-single-positive T cells in thymus and spleen. However, CD28-deficient mice had decreased CD4 CD25 T cells in spleen compared with wild-type mice, and CD7/CD28-double-deficient mice had decreased numbers of CD4 CD25 T cells in both thymus and spleen compared with both wild-type and CD28-deficient mice. Functional studies demonstrated that CD4 CD25 T cells from CD28-deficient and CD7/CD28-double-deficient mice could mediate suppression of CD3 mAb activation of CD4 CD25- wild-type T cells, but were less potent than wild-type CD4 CD25 T regulatory cells. Thyroiditis developed in aged CD7/CD28-double-deficient mice (>1 year) that was not seen in age-matched control mice or single CD7- or CD28-deficient mice, thus suggesting in vivo loss of T regulatory cells allowed for the development of spontaneous thyroiditis. Taken together, these data demonstrated collaborative roles for both CD7 and CD28 in determination of number and function of CD4 CD25 T regulatory cells in the thymus and peripheral immune sites and in the development of spontaneous thyroiditis.
MeSH Terms
- Aging
- Animals
- Antibodies, Monoclonal
- Antigen-Presenting Cells
- Antigens, CD
- Antigens, CD7
- B7-1 Antigen
- B7-2 Antigen
- CD28 Antigens
- CD3 Complex
- CD4-Positive T-Lymphocytes
- CD8-Positive T-Lymphocytes
- Cell Division
- Concanavalin A
- Cytokines
- Down-Regulation
- Homeostasis
- Immunophenotyping
- Leukocyte Count
- Lipopolysaccharides
- Lymphocyte Count
- Lymphopenia
- Male
- Membrane Glycoproteins
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Receptors, Interleukin-2
- Spleen
- T-Lymphocyte Subsets
- Thymus Gland
- Thyroiditis
Substantial changes in both representation and function of T lymphocyte subsets have been reported with advancing age. However, till now, no systematic studies focused on age-dependent changes in the expression intensity of the major T lymphocyte surface receptors. The present study was undertaken in order to establish age-related differences in lymphocyte subpopulations by simultaneously measuring three surface antigens in young and elderly people. Peripheral blood T cell subsets from 20 healthy elderly individuals and 15 healthy young adult donors were examined by means of a quantitative three-color flow cytometry method. Activated (HLA-DR ) and memory (CD45RO ) T cells, CD3 CD7- T lymphocytes, and cells expressing natural killer (NK) markers (CD3-CD56 NK cells and CD3 CD56 T lymphocytes) were expanded, whereas T lymphocytes expressing the adhesion molecule CD62L were lower in elderly compared with young donors. In addition to alterations in the percentages of T cell subsets during senescence, several changes in the intensity expression of T cell antigens were also detected. CD3 antigen expression was downregulated on total T lymphocytes as well as on the memory T cell subset, while CD56 T cells exhibited increased CD3 levels. Moreover, CD2 expression, unchanged on NK cells, was upregulated on T lymphocytes from elderly subjects. CD3 CD7- T cells exhibited increased expression of CD8 antigen, while the intensity expression of HLA-DR on activated T cells and CD7 on both T and NK lymphocytes was decreased. T cells from elderly subjects also exhibited higher expression of CD50 and CD62L adhesion molecules as compared with young ones. These T cell antigen expression modulations during senescence, in addition to the alteration in the frequency of the various T lymphocyte subsets, could contribute to the complex remodeling of the immune function characteristic of the elderly.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Antigens, CD
- Female
- Flow Cytometry
- Humans
- Immunologic Memory
- Immunophenotyping
- Killer Cells, Natural
- Lymphocyte Activation
- Male
- Middle Aged
- T-Lymphocyte Subsets
We observed three cases of acute leukemia with trisomy 10 ( 10) as the sole abnormality, two were adult patients with ANLL (subtype M0 and M1 respectively), and the third that of a child with ALL. The literature describes nine additional cases, four with ALL (all of whom were children) and five with ANLL (all of whom were adults). Cell marker studies on the ANLL cases showed a common positivity for CD7 and CD33 in our two cases, as well as in four of the previously reported cases, whereas in ALL the only two informative cases were classified as early pre-B ALL. There appears to be an age-related pattern in the specificity of the leukemic lineage. Trisomy 10 appears to be associated exclusively with ALL in children and with ANLL (usually M0-M1) in adults. The prognosis appears to be also divided between the two groups, being good in the pediatric group and moderate in the adult group.
MeSH Terms
- Aged
- Aging
- Bone Marrow
- Child, Preschool
- Chromosomes, Human, Pair 10
- Female
- Humans
- Leukemia, Myeloid, Acute
- Male
- Middle Aged
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Prognosis
- Trisomy
CD7 is one of the major surface antigens expressed very early during T cell ontogeny. Lack of CD7 expression on mature T cells is regarded as a classical feature of malignant T cells in certain forms of cutaneous T cell lymphoma. Previously, we identified a CD7- subset of peripheral blood T lymphocytes in normal human individuals. In this study we determined the portion of CD7- T cells in the peripheral blood of healthy volunteers ranging in age from 8 months to 90 years (n = 85) and in cord blood of full-term infants (n = 14). Furthermore, this CD7- subset was characterized in detail by the use of MoAbs and three-colour flow cytometry. In cord blood no CD7- T cells could be detected. After birth, percentage and absolute number of CD7- T cells increased with age. Independently of age, most CD7-CD3 cells belonged to the CD4 subpopulation. Focusing on the latter we could demonstrate the predominance of the CD45RO CD45RA- phenotype in the CD7- subset. Furthermore, CD7- T cells contained a higher number of cells expressing activation markers and the CD57 antigen, but a reduced number of CD62L cells in comparison with CD7 T cells.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Antigens, CD
- Antigens, CD7
- Antigens, Differentiation, T-Lymphocyte
- CD4-Positive T-Lymphocytes
- Child
- Child, Preschool
- Female
- HLA-DR Antigens
- Humans
- Infant
- Infant, Newborn
- Leukocyte Common Antigens
- Male
- Middle Aged
- T-Lymphocyte Subsets
Children with ALL diagnosed at less than 2 years of age have a poor prognosis when compared with older children. In an effort to identify biologic features of ALL in children less than 2 that might explain this difference, we performed extensive immunophenotypic and molecular genetic analyses on a series of patients. For comparison purposes patients were divided into four groups: CALLA- (CD10-) infants less than 2 years of age at diagnosis (n = 10), CALLA- children greater than 2 years of age at diagnosis (n = 10), CALLA infants (less than 2 years, n = 21) and CALLA children (older than 2 years, n = 21). No immunophenotyping differences in CALLA- or CALLA subgroups were identified when cases less than 2 were compared with cases greater than 2 years of age at diagnosis. The most interesting results were in the CALLA- group where 94% of the samples expressed the B cell antigen CD19 but 27% co-expressed CD7. Double labeling experiments confirmed leukemic blast cells co-expressed CD19 and CD7. The double-labeled cells represent either leukemic conversion of a precursor cell which has not yet committed to B or T cell lineage or aberrant expression of these antigens. Molecular genetic studies demonstrated that all samples, regardless of the patients' age or immunophenotype, had rearrangement of the Ig heavy chain gene. The most striking molecular results were in CALLA- patients; in patients less than 2 at diagnosis neither the beta- nor the gamma-chain gene of the T cell receptor (TCR) was rearranged, whereas DNA from 5 of 10 patients over the age of 2 demonstrated beta- or gamma-chain TCR gene rearrangements. The percentage of CALLA cases under the age of 2 years with rearrangements in TCR genes is less than that found in CALLA cases over the age of 2 years. The finding of no TCR rearrangements in CALLA- ALL and a decreased number of gamma-TCR rearrangements in CALLA cases under the age of 2 suggest that age may affect TCR gene rearrangements in lymphoblasts. The molecular differences in TCR gene rearrangements do not appear to correlate with the response to therapy.
MeSH Terms
- Aging
- Antigens, Differentiation
- Antigens, Differentiation, B-Lymphocyte
- Antigens, Neoplasm
- B-Lymphocytes
- Biomarkers, Tumor
- Burkitt Lymphoma
- Gene Rearrangement, T-Lymphocyte
- Hematopoietic Stem Cells
- Humans
- Infant
- Neprilysin
- Prognosis
- Receptors, Antigen, T-Cell