The Journal of Immunology, Vol 144, Issue 7 2550-2557, Copyright © 1990 by American Association of Immunologists

ARTICLES

Induction of proliferation of human follicular (B type) lymphoma cells by cognate interaction with CD4+ T cell clones

DT Umetsu, L Esserman, TA Donlon, RH DeKruyff and R Levy
Department of Medicine, Stanford University School of Medicine, CA 94305.

We examined stimuli which are required for the induction of in vitro proliferation of follicular lymphoma cells, a low grade non-Hodgkin's B cell lymphoma characterized by a specific chromosomal translocation, t(14;18)(q32;q21), and by in vivo growth of the lymphoma cells in germinal center-like follicles infiltrated with CD4+ T cells. The purified follicular lymphoma cells, which are morphologically uniform, small, and dense, did not respond to stimulation with soluble lymphokines in the absence of T cells. Vigorous in vitro proliferation of follicular lymphoma cells was induced, however, when the follicular lymphoma cells were cultured with a CD4+ T cell clone which recognized alloantigens expressed by the lymphoma cells. This response required B- T cell contact, and was inhibited by anti-class II but not by anti- class I MHC mAb, indicating that these neoplastic B cells behaved as normal B cells and responded to normal activation and differentiation signals from T cells. After the cognate B lymphoma-T cell interaction occurred in culture, addition of IL-2 or IL-4 enhanced the proliferation of the tumor cells. These results, with a monoclonal and homogeneous population of B cells, affirm the idea that cognate interaction between B cells and Th cells is required for the effective activation of resting B cells. Moreover, these results suggest that a critical host-tumor interaction occurs in vivo, and that the polyclonal CD4+ T cells that infiltrate follicular lymphomas play a role in sustaining rather than inhibiting tumor growth in vivo. If so, therapies directed not only against the neoplastic cell but also against specific T cells and their cognate interactions with tumor cells may have a rationale.

This article has been cited by other articles:

				K. R. Calvo, B. Dabir, A. Kovach, C. Devor, R. Bandle, A. Bond, J. H. Shih, and E. S. Jaffe IL-4 protein expression and basal activation of Erk in vivo in follicular lymphoma Blood, November 1, 2008; 112(9): 3818 - 3826. [Abstract] [Full Text] [PDF]

				M. M. Zangani, M. Froyland, G. Y. Qiu, L. A. Meza-Zepeda, J. L. Kutok, K. M. Thompson, L. A. Munthe, and B. Bogen Lymphomas can develop from B cells chronically helped by idiotype-specific T cells J. Exp. Med., May 14, 2007; 204(5): 1181 - 1191. [Abstract] [Full Text] [PDF]

				T. Alvaro, M. Lejeune, M.-T. Salvado, C. Lopez, J. Jaen, R. Bosch, and L. E. Pons Immunohistochemical Patterns of Reactive Microenvironment Are Associated With Clinicobiologic Behavior in Follicular Lymphoma Patients J. Clin. Oncol., December 1, 2006; 24(34): 5350 - 5357. [Abstract] [Full Text] [PDF]

				J. Carreras, A. Lopez-Guillermo, B. C. Fox, L. Colomo, A. Martinez, G. Roncador, E. Montserrat, E. Campo, and A. H. Banham High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma Blood, November 1, 2006; 108(9): 2957 - 2964. [Abstract] [Full Text] [PDF]

				J. L. Szocinski, A. R. Khaled, J. Hixon, D. Halverson, S. Funakoshi, W. C. Fanslow, A. Boyd, D. D. Taub, S. K. Durum, C. B. Siegall, et al. Activation-induced cell death of aggressive histology lymphomas by CD40 stimulation: induction of bax Blood, June 17, 2002; 100(1): 217 - 223. [Abstract] [Full Text] [PDF]

				S. Oeschger, A. Brauninger, R. Kuppers, and M.-L. Hansmann Tumor cell dissemination in follicular lymphoma Blood, March 15, 2002; 99(6): 2192 - 2198. [Abstract] [Full Text] [PDF]

				E. Tartour, F. Fossiez, I. Joyeux, A. Galinha, A. Gey, E. Claret, X. Sastre-Garau, J. Couturier, V. Mosseri, V. Vives, et al. Interleukin 17, a T-cell-derived Cytokine, Promotes Tumorigenicity of Human Cervical Tumors in Nude Mice Cancer Res., August 1, 1999; 59(15): 3698 - 3704. [Abstract] [Full Text] [PDF]

				P. P. Lee, D. Zeng, A. E. McCaulay, Y.-F. Chen, C. Geiler, D. T. Umetsu, and N. J. Chao T Helper 2-Dominant Antilymphoma Immune Response Is Associated With Fatal Outcome Blood, August 15, 1997; 90(4): 1611 - 1617. [Abstract] [Full Text] [PDF]