Association between Sézary T Cell‐activating Factor, Chlamydia pneumoniae, and Cutaneous T Cell Lymphoma

Abstract

Séezary 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.

A novel KIR-associated function: evidence that CpG DNA uptake and shuttling to early endosomes is mediated by KIR3DL2

“…A role in the pathogenesis of Sézary T-cell lymphoma has been proposed for skin-associated microbes such as Staphylococcus aureus 36 and Chlamydia. 37 Other studies reported an association between this lymphoma and cytomegalovirus 38 or Epstein-Barr virus infections. 39 In this context, microbial ODN-mediated cell triggering may induce uncontrolled proliferation of KIR3DL2 ϩ Sézary T cells, possibly representing an early event in the tumorigenic process leading to the malignant lymphoma.…”

Role of Bacteria in Oncogenesis

“…Other associations between bacterial infection and B-cell proliferation have been examined in a few studies. Among these, H. pylori seropositivity in childbearing women has been linked with childhood acute lymphocytic leukemia in their offspring (147), and Chlamydia pneumonia has been associated with lung MALT lymphoma (44) and the Séz-ary syndrome (5). However, the lack of sufficient data precludes any conclusions about these associations at this time.…”

Mycosis fungoides: is it a Borrelia burgdorferi-associated disease?

“…It has also been suggested that bacterial agents, such as Staphylococcus aureus (Tokura et al, 1992;Jackow et al, 1997) or Chlamydia pneumoniae (Abrams et al, 2001), might contribute to MF pathogenesis by acting as persistent antigens, thus exacerbating and/or perpetuating chronic T-cell expansion and cutaneous inflammation.…”