T Helper Cell Activation in B-Cell Lymphomas
Authors: H. Bosshart, Stephen M. Ansell, Diane F. Jelinek, Peter J. Wettstein, Thomas E. Witzig
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.12.2904 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12065568 T Helper Cell Activation in B-Cell Lymphomas H. BosshartxH. BosshartSearch for articles by this author Stephen M. AnsellxStephen M. AnsellSearch for articles by this author , Diane F. JelinekxDiane F. JelinekSearch for articles by this author , Peter J. WettsteinxPeter J. WettsteinSearch for articles by this author , Thomas E. WitzigxThomas E. WitzigSearch for articles by this author Show More University Hospital, Zurich, SwitzerlandMayo Clinic, Rochester, MN https://doi.org/10.1200/JCO.2002.20.12.2904 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse15062002In Reply:We read with interest the correspondence from Dr H. Bosshart describing a significant difference in the percentage of CD4+ T cells in follicular lymphoma and diffuse large-cell lymphoma when compared with reactive lymph nodes and Hodgkin’s lymphoma. We also noted the significantly higher percentage of CD69+ T-helper cells found in the various B-cell lymphoma specimens when compared with the reactive nodes and that the percentage of CD69+ T cells in the various types of B-cell malignancies was similar. We agree that CD69+ CD4+ cells are a feature of the T-helper cells in B-cell malignancies and have also found that the majority of CD4+ T cells in B-cell lymphomas are CD69+. Although we have also consistently found the percentage of CD69+ T cells in B-cell lymphomas to be approximately 40% to 70%, we have found that the absolute numbers of these T cells may vary greatly. Therefore, although we agree that a generalization of the quantitative concept of numbers of infiltrating CD4+ T-cells to other B-cell malignancies such as Hodgkin’s lymphoma (where T cells may play a different role) may not be appropriate, we do feel that the number of infiltrating CD4+ T cells in both large-cell and follicular lymphoma has significance. We have previously shown that increased CD4+ cells in follicular lymphoma predicts patient outcome1 and Xu et al2 have confirmed our observation that the number of tumor infiltrating CD4+ T cells has prognostic significance in large-cell lymphoma.What is unknown, however, is whether the increased number of infiltrating cells is truly indicative of effective immune surveillance. As stated by Dr Bosshart, the interaction between the immune system, particularly CD4+ T cells, and the malignant clone is very complex. In our experience, it has been difficult to determine whether the increased numbers of CD4+ T cells present in lymphoma tissue is indicative of an antitumor immune response or just a nonspecific representation of the patient’s overall immune status. We have investigated the phenotype of infiltrating CD4+ T cells but have not been able to identify a predominant CD4+ T-cell subset in areas of B-cell lymphoma. Using flow cytometry, we have assessed the percentage and number of CD4+ T cells in lymphoma specimens that express gamma interferon, interleukin-4, CXCR5, or CD25, to specifically evaluate the presence of Th1, Th2, TFH cells (Th cells with B-cell helper function)3 and regulatory T cells.4 In 30 lymphoma specimens with various indolent and aggressive histologies, the median number of Th1, Th2, TFH, and regulatory T cells expressed as a percent of the total CD4+ cells was 12.5% (range, 1% to 51%), 2.5% (range, 0.7% to 5.9%), 10.3% (range, 2.5% to 42.7%), and 4.4% (range, 2.1% to 14.6%), respectively. In 10 of these patients, we also evaluated the T-cell receptor repertoire of the CD4+ cells using T-cell spectratyping and found that the T-cell repertoire was normally diverse in all patients.These studies would suggest that the activated T cells present in lymphoma specimens are more likely to represent a nonspecific infiltration of immune cells rather than a specific antitumor clonal expansion, but further studies to evaluate the nature of infiltrating CD4+ T cells and to increase their tumor-specific activity are clearly needed.1. Ansell SM, Stenson M, Kurtin PJ, et al: Infiltration by activated CD4+ T-cells is an important determinant of prognosis in low grade and intermediate grade B-cell lymphomas. Proc Am Soc Clin Oncol 18:: 15,,1999 (abstr 15) Google Scholar2. Xu Y, Kroft SH, McKenna RW, et al: Prognostic significance of tumour-infiltrating T lymphocytes and T-cell subsets in de novo diffuse large B-cell lymphoma: A multiparameter flow cytometry study. Br J Haematol 112:: 945,2001-949, Crossref, Medline, Google Scholar3. Breitfeld D, Ohl L, Kremmer E, et al: Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med 192:: 1545,2000-1552, Crossref, Medline, Google Scholar4. Sakaguchi S, Sakaguchi N, Shimizu J, et al: Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: Their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev 182:: 18,2001-32, Crossref, Medline, Google Scholar