Immunologic profile in patients with Hodgkin's disease in complete remission

Abstract

Mononuclear cell subsets in peripheral blood, in vitro production of interleukin-2 (IL-2) and gamma interferon (IFN gamma), spontaneous cell-mediated cytotoxicity (SCMC) and circulating levels of Type I IFN, neopterin, beta-2 microglobulin (B2-M), immunoglobulins and complement fractions were studied in 33 patients with Hodgkin's disease (HD) in complete remission. The mean percentages, but not the absolute numbers, of T-lymphocytes expressing pan-T markers (OKT11, OKT3, ER, E-AET R) were significantly decreased compared with control values. Furthermore, patients showed a selective loss of OKT4+ cells, as well as increased percentages and numbers of Leu7+ and OKIa+ lymphocytes, and of OKM1+, LeuM2+, and LeuM3+ cells. OKT4+ cell depletion was a characteristic of patients with shorter time since beginning of remission as well as of those with nodular sclerosis (NS), mixed cellularity Hodgkin's disease (MC-HD), and systemic symptoms at diagnosis. Multifactorial statistical analysis carried out to investigate the effect of disease characteristics and the time since remission began on peripheral mononuclear blood cell (PMBC) subsets showed that histologic condition was the single best predictor of T-cell pool or OKT4+ cell subset size. Time since remission duration and other disease-related factors determined differences in the percentages, but not in the absolute numbers, of T-cell fractions. In addition, neither the disease features nor the time since remission duration determined significant differences in the absolute number of non-T-mononuclear cells in the various patient groups. Patients displayed decreased in vitro synthesis of IL-2 and IFN gamma. The values of SCMC, Type I IFN, neopterin, B2-M, immunoglobulins, and complement fractions did not differ greatly from those of controls.

Correlation of blood lymphocyte CTLA‐4 (CD152) induction in Hodgkin's disease with proliferative activity, interleukin 2 and interferon‐gamma production

“…Our findings suggest that the upregulation of downregulatory CTLA-4 antigen on PBL-T in HD may not be a fully reversible phenomenon and, in agreement with others (Liberati et al, 1987) and our own studies (Frydecka et al, 1999), indicate that HD patients continue to have immune abnormalities even after successful treatment. The mechanisms underlying these findings are unknown and require further studies.…”

Expression of the signal transduction molecule ζ in peripheral and tumour‐associated lymphocytes in Hodgkin's disease in relation to the Epstein–Barr virus status of the tumour cells

“…tuberculosis, viral and fungal infections) has been found in HD patients together with inferior responses to many recall antigens (Reed, 1902; Gaines et al , 1973; Armstrong et al , 1990). In addition to a variable lymphocytopenia, peripheral blood lymphocytes (PBLs) of HD patients exhibit markedly decreased cytokine production and decreased proliferative responses after antigen or mitogen stimulation in vitro (Dorreen et al , 1982; Ford et al , 1984; Liberati et al , 1987; Cimino et al , 1988; Tullgren et al , 1991). Epstein–Barr virus (EBV), a ubiquitous human herpesvirus eliciting CD8 + cytotoxic T‐lymphocyte (CTL) responses (Rickinson et al , 1981), is present in Hodgkin and Reed‐Sternberg (HRS) cells in ≈ 40% of cases (EBV + HD) (Weiss et al , 1989; Herbst et al , 1990).…”