Displacement of T Lymphocytes with the ‘Helper/Inducer’ Phenotype from Peripheral Blood to Lymphoid Organs in Untreated Patients with Hodgkin's Disease

Abstract

A panel of previously characterized monoclonal antibodies: B67.6, OKT3, OKT4, B53.4, Leu3a, OKT8, Leu2a, OKM1, M12 and B52.1 were used as a probe to assess mononuclear cells in peripheral blood (PB), lymph nodes (LN) and spleens of untreated patients with Hodgkin's disease (HD). The mean % and absolute number of T lymphocytes were significantly decreased in PB of HD patients when compared with control values. Reduction of circulating T lymphocytes reflected the selective loss of cells showing the ‘helper/inducer’ (‘H/I’) phenotype. In fact, a lower number of these cells was demonstrated in HD patients with advanced disease and, even though to a lesser extent, in those with localized disease. In contrast, decreased values of T cells with the ‘cytotoxic/syppressor’ (‘C/S’) phenotype were only found in patients with advanced disease, showing pan‐lymphocytopenia. Unlike PB, LN and spleens involved by HD usually showed increased %s of T lymphocytes, especially of those possessing the ‘H/I’ phenotype. The displacement of T lymphocytes with ‘H/I’ phenotype from PB to lymphoid organs further supports the possibility of a chronic immune response against abnormal cells or unknown antigens in the affected organs of patients with HD.

HIV-1–related Hodgkin lymphoma in the era of combination antiretroviral therapy: incidence and evolution of CD4+ T-cell lymphocytes

“…27 The mechanisms leading to peripheral lymphocytopenia are not well understood, and several factors, including immunosuppressive effects of cytokines and redistribution of lymphocytes from the periphery into tumor tissue, might be involved. 41,43,44 Our results confirm previous observations from the Swiss HIV Cohort Study 17,28 and indicate that declining CD4 cell counts in patients responding to cART may represent early signs of HL. 45 Further research is required to clarify to what extent this observation is specific to HL, or a more general phenomenon in patients developing opportunistic events.…”

Clinical Presentation, Treatment, and Outcomes Among 65 Patients with HIV-Associated Lymphoma Treated at the University of North Carolina, 2000–2010

“…4 Lymphocytopenia occurs frequently at HL diagnosis even among HIV-uninfected individuals, correlates with poor survival, and remains poorly understood with postulated mechanisms including cytokine-induced immunosuppression and redistribution of lymphocytes from the periphery into tumor tissue. 4,[26][27][28][29][30][31] In addition, the observation that BL and HL incidence in some epidemiologic studies is higher in HIV-infected persons with higher CD4 counts also remains largely unexplained. Proposed mechanisms for HL include chemokine-induced recruitment of CD4 cells to germinal centers inhabited by EBV-transformed lymphocytes, which may promote survival of malignant lymphocytes by protecting them against immune surveillance, and also interactions between CD40 ligand on activated CD4 cells and CD40 receptors on malignant Reed-Sternberg cells, which serve to activate the nuclear factor-jB pathway.…”

HIV-associated Hodgkin lymphoma during the first months on combination antiretroviral therapy

“…8 HL in the general population that is unrelated to HIV is associated with elevated circulating levels of immunoregulatory T cells, [24][25][26] as well as with T-cell and total lymphopenia, 27 perhaps the result of chemoattraction of T cells from the blood to tumorassociated malignant Hodgkin/Reed-Sternberg cells. [28][29][30] Chemokines CCL22 and especially CCL17 have been specifically implicated, 28,29,31 but other chemokines may also be involved. 31 To our knowledge, chemokine levels in HIV-associated HL have not been evaluated by immunohistochemistry or serology.…”