Reduced cellular immunity to varicella zoster virus during treatment for acute lymphoblastic leukemia of childhood:In Vitro studies of possible mechanisms

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Abstract
To determine the effect of antileukemic therapy on preexisting immunity to varicella zoster virus, we studied 20 children with acute lymphoblastic leukemia maintained in complete continuous remission for greater than 1 year. Cellular immunity was tested by lymphocyte proliferation in response to varicella antigen. Antiviral antibody was measured using the fluorescent antibody to membrane antigen technique. Reduced lymphocyte proliferation was found in 9 of 16 seropositive patients when compared to an age-related control group. On the other hand, antibody titers in patients receiving chemotherapy remained positive and were essentially unchanged from pretreatment values. Shingles occurred in two of nine children with diminished and none of seven patients with normal cellular immunity, suggesting that proliferative responses to varicella antigen may have predicative value in identifying patients at risk for viral reactivation. Additional studies were done to determine if defective antigen presentation or reduced lymphocyte responder-cell frequency could account for the subnormal proliferative responses. Intact presentation of varicella antigens by patient mononuclear cells to parental, virus-specific T-cell blasts suggested that antigen processing was not defective. However, varicella-specific responder-cell frequencies measured by limiting dilution analysis were found to be depressed in most patients, including some with normal proliferative responses. Our findings indicate that therapy for acute lymphoblastic leukemia in children can be associated with depressed cell-mediated immunity to varicella zoster virus even though patients remain seropositive. Further studies suggest that while monocyte-mediated antigen presentation remains intact, virus-specific lymphocyte numbers decline and probably contribute to decreased cellular immunity to varicella zoster virus in children being treated for leukemia.