RHESUS THYMIC LIVER XENOGRAFTS IN SEVERE COMBINED IMMUNODEFICIENT MICE - IMMUNOLOGICAL RECONSTITUTION AND INTRATHYMIC INFECTION WITH SIMIANIMMUNODEFICIENCY VIRUS/

By serving as host recipients of xenografts from both humans and anima ls, severe combined immunodeficient (SCID) mice have become valuable t o many laboratories interested in examining the pathophysiology of dif ferent diseases. To gain insight into the usefulness of the SCID mutat ion in retrovirus research, rhesus monkey fetal hematolymphoid tissues (liver and thymus) were used to construct a SCID-rhesus chimeric mous e (SCID-rh) and were engrafted in the renal capsule. The size and matu ration of the thymic engrafts were monitored grossly, histologically, and immunologically. SCID mice were tolerant to rhesus tissues, and th ymic engrafts contained thymocytes at different stages of maturation a nd differentiation that had morphologic features similar to age-matche d rhesus thymus. Mature single positive CD2+, CD4+, and CD8+ T lymphoc ytes that were phenotypically similar to rhesus T lymphocytes were pre sent at low levels (2% to 5%) in the peripheral blood and at moderatel y higher levels (7% to 15%) in the spleens of SCID-rh mice obtained be tween 12 and 15 weeks after thymus/liver engraftment. Within 3 weeks a fter engraftment, >85% of the thymocytes in the thymic engrafts were i mmature double positive CD4+CD8+ T cells. The highest number of positi ve cells were seen in thymic engrafts obtained at 12 to 18 weeks. Duri ng these weeks, >90% of the cells were double positive (CD2+CD4+, CD2CD8+, and CD4+CD8+). After infection of the engrafted thymus tissue wi th simian immonodeficiency virus (SIV(mac)239), PCR analysis revealed successful viral infection of engrafts at 2 and 4 weeks after infectio n. No significant histopathologic and flow cytometric changes were obs erved in the thymic engrafts at 2 and 4 weeks after infection. An unre lated lesion of thymic lymphomas involving the SCID host thymus was se en in 12% of the mice. The data presented herein suggest that the SCID -rh is a valuable model for specific studies related to thymus-retrovi rus interaction and that it could be used for further studies. The res ults are discussed in relation to current knowledge of thymus involvem ent during simian and human immunodeficiency virus infection.