GVHR elicited by products of class I or class II loci of the MHC: analysis of the response of mouse T lymphocytes to products of class I and class II loci of the MHC in correlation with GVHR-induced mortality, medullary aplasia, and enteropathy.

Abstract

A lethal graft-vs-host reaction (GVHR) was elicited by the injection into irradiated (700 rad) mice, reconstituted with T-depleted bone marrow cells (BM), of T lymphocytes incompatible for different loci of the major histocompatibility complex (MHC). The number of T cells needed to kill more than 50% of the recipients by day 40 was about 10(6) for GVHR elicited across the product of the K, D, or E locus, but about 10(5)--10--fold less-when the A locus was involved. The mortality was associated with a medullary aplasia in all strain combinations, but enteropathy was observed only in GVHR elicited by the products of class II, and not class I, loci. Mortality and medullary aplasia were diminished or absent in recipients reconstituted with BM cells from T cell donors instead of cells of the host genotype, which suggests a direct (cytolytic) T-hematopoietic cell interaction. Lymphoproliferation was evident within the host spleen and lymph node 5 days after injection of T lymphocytes incompatible for class II but not class I loci. Spleens from mice suffering from a lethal GVHR were examined by culture in limiting dilution to evaluate the frequency of anti-host T cells and to derive anti-host T cell clones and lines, whose properties were explored. In the GVHR elicited across the A or E region of the MHC, examined between days 7 and 19, a high frequency (10(-2] of anti-host cells was observed. The polyclonal cell lines isolated (16) all displayed MLR responsiveness, antigen-driven IL 2 production, and cytolysis for LPS blasts of the host genotype. However, among 13 clones isolated, two categories were observed: Lyt-2-, which were MLR responders and IL 2 producers (four of 13), and Lyt-2+, which were cytolytic but neither MLR responders nor IL 2 producers (nine of 13). In the GVHR elicited by the K or D region, examined between days 7 and 90, the frequency of anti-host cells was low (10(3) to 10(4], with a tendency to decrease during the progression of the disease. The lines (11) or clones (26) isolated from different mice were all Lyt-2+ and strongly cytolytic but proliferated poorly and produced no IL 2 in MLR. These findings suggest that the Lyt-2+ lymphocytes, recognizing the products of the class I loci, function in vivo without proliferation and without requiring helper T cells. Cell lines specific for class I or class II loci of the MHC produced interferon and colony-stimulating factors.