Association between Sézary T cell-activating factor, Chlamydia pneumoniae, and cutaneous T cell lymphoma.
Sézary T cell-activating factor (SAF) was originally defined as an inducer of functional interleukin-2 (IL-2) receptors on normal and malignant T cells in patients suffering from Sézary syndrome. In fact, a combination of SAF and IL-2 stimulated the propagation of T cell lines from the peripheral blood mononuclear cells (PBMC) of those patients, with approximately one third of those cell lines containing the predominant malignant clone as determined via cytogenetic and/or T cell receptor gene rearrangement analysis. Although the primary source of SAF was mitogen-stimulated PBMC of a patient with Sézary syndrome, we were unable to isolate the gene encoding SAF from eukaryotic libraries. However, we observed SAF activity in the cytoplasm of one of the malignant cell lines in a complex containing RNA and DNA. This observation led us to consider the possibility that SAF is not of eukaryotic origin. Intracellular pathogens replicate in the cytoplasm of host cells and contain proteins, DNA, and RNA. Using a panel of antichlamydial antibodies with confirmation from polymerase chain reaction primers, we found that most patients with mycosis fungoides were positive for these determinants. Immunoelectron microscopy and protein blotting further confirmed antibody reactivity. We showed that Chlamydia pneumoniae were capable of infecting normal human keratinocytes in culture. We also demonstrated that C. pneumoniae antigen expression was associated with active disease because these determinants were not expressed after psoralen and ultraviolet A therapy. We hypothesize that chronic infection by C. pneumoniae leads to expansion of C. pneumoniae-specific T cells, thereby potentiating the development of cutaneous T cell lymphoma.
Abrams
J T
JT
Meniscus Limited, West Conshohocken, Pennsylvania 19428-2935, USA. tabrams@meniscus.com
Balin
B J
BJ
Vonderheid
E C
EC
D000942:Antigens, Bacterial / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D023521:Chlamydophila Infections / Q000378:metabolism / Q000382:microbiology*; D016993:Chlamydophila pneumoniae / Q000276:immunology / Q000302:isolation & purification*; D002908:Chronic Disease; D002999:Clone Cells; D005544:Forecasting; D006133:Growth Substances / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000382:microbiology; D008213:Lymphocyte Activation; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism / Q000382:microbiology*; D009000:Monocytes / Q000382:microbiology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D012878:Skin Neoplasms / Q000378:metabolism / Q000382:microbiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000942:Antigens, Bacterial; D006133:Growth Substances; D015375:Receptors, Interleukin-2