EPIDEMIOLOGY OF HD IN TWINS--INFECTIONS/T-CELL FUNCTION

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Several lines of epidemiologic evidence suggest that young adult Hodgkin's disease is determined by late exposure to one or more infectious agents, possibly including Epstein-Barr virus, and other lines indicate that this conditions occurs with unexpectedly high frequency in the blood relatives of other HD cases. Clinical and laboratory studies point to a T-helper cell functional abnormality as the primary deficit in this disease. It is becoming clear that in both mouse and man T-helper cells (Th cells) clone more or less -dichotomously into two types, designated Th1 and Th2, which can be differentiated on the basis of the cytokine secretion pattern, which are induced by different exogenous agents, which may be mutually inhibitory, and which appear to serve different functions. Th1 cells promote the cell-mediated immune response, and Th2 cells promote activation of humoral immunity. The EBV genome contains a component that may simulate certain Th2 functions. We hypothesize that HI) occurs in a condition of suppressed cell-mediated immunocompetence, induced by a genetically determined predominance of Th2 function, with consequent suppression of Th1 function, with or without synergistic suppression of Th1 as a result of EBV infection, and with or without exposure to other infectious agents, following the polio model of age-specific disease susceptibility. We propose to study subsets of twin pairs discordant for HI) by I) comparing the Th secretion profiles of cases and their healthy identical co-twins to that of unrelated persons, 2) comparing the anti-EBV antibody titers of cases their healthy identical co-twins with those of healthy unrelated persons, and 3) comparing the V-Beta T-cell receptor repertoire of cases and their healthy identical co-twins of cases to those of unrelated persons.