Abstract

Large granular lymphocyte (LGL) leukemia results from chronic proliferation of either CD3- or CD3+ LGL. The two different subsets of leukemic LGL offer an opportunity to examine the activation of the two classes of non- MHC-restricted cytotoxic lymphocytes, ie, CD3- LGL (natural killer cells) and CD3+ LGL (non-MHC-restricted cytotoxic T lymphocytes). The mechanism of activation leading to proliferation (Specific Aim #1) and cytotoxicity (Specific Aim #2) will be examined. Activation of leukemic LGL will be produced using anti-CD3 monoclonal antibody or lymphokines such as IL-2, IL-4, or IL-6. Lymphokine secretion, expression of lymphokine cell surface receptors, and expression of lymphokine gene transcripts will be measured before and after activation. These studies will allow evaluation of 1) whether aberrant or autocrine secretion of lymphokines such as IL-6 is associated with pathogenesis of LGL, 2) whether the mechanism of activation differs for CD3- and CD3+ LGL, 3) whether the mechanism of proliferative activation differs from that producing activation of cytotoxicity, and 4) whether anti-CD3 monoclonal antibody, IL-2, IL-4, and IL-6 provide different triggering signals for activation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA046903-02
Application #
3190401
Study Section
Pathology B Study Section (PTHB)
Project Start
1990-08-01
Project End
1992-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109

  Publications

Starkebaum, G; Loughran Jr, T P; Gaur, L K et al. (1997) Immunogenetic similarities between patients with Felty's syndrome and those with clonal expansions of large granular lymphocytes in rheumatoid arthritis. Arthritis Rheum 40:624-6
Kingreen, D; Dalal, B I; Heyman, M et al. (1995) Lymphocytosis of large granular lymphocytes in patients with Hodgkin's disease. Am J Hematol 50:234-6
Davey, M P; Starkebaum, G; Loughran Jr, T P (1995) CD3+ leukemic large granular lymphocytes utilize diverse T-cell receptor V beta genes. Blood 85:146-50
Gentile, T C; Loughran Jr, T P (1995) Interleukin-12 is a costimulatory cytokine for leukemic CD3+ large granular lymphocytes. Cell Immunol 166:158-61
Zambello, R; Loughran Jr, T P; Trentin, L et al. (1995) Serologic and molecular evidence for a possible pathogenetic role of viral infection in CD3-negative natural killer-type lymphoproliferative disease of granular lymphocytes. Leukemia 9:1207-11
Litam, P P; Loughran Jr, T P (1995) Clostridium septicum bacteremia in a patient with large granular lymphocyte leukemia. Cancer Invest 13:492-4
Loughran Jr, T P; Kidd, P G; Starkebaum, G (1994) Treatment of large granular lymphocyte leukemia with oral low-dose methotrexate. Blood 84:2164-70
Loughran Jr, T P; Sherman, M P; Ruscetti, F W et al. (1994) Prototypical HTLV-I/II infection is rare in LGL leukemia. Leuk Res 18:423-9
Voltarelli, J C; Loughran Junior, T P (1994) Expansion of a subset of TCR gamma/delta human lymphocytes from various lymphoid organs cultured with recombinant IL-2. Braz J Med Biol Res 27:709-18
Loughran Jr, T P; Shriver, M K (1994) Seroprevalence of HTLV-I and HTLV-II in marrow transplant recipients. Bone Marrow Transplant 14:433-6

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