Evidence of cytotoxic T-cell destruction of epidermal cells in human graft-vs-host disease. Immunohistology with monoclonal antibody TIA-1.
A newly described mouse monoclonal IgG1 antibody, TIA-1, binds serine esterase-positive granule membranes of cytotoxic human T cells and is a candidate for an effector molecule involved in T-cell cytolytic mechanisms analogous to those of the perforin system. We performed immunohistologic studies on frozen human skin (n = 5) and lip (n = 21) sections as well as on control frozen sections of tonsils, purified cytolytic T (CD8) cells, and B cells using an indirect immunoperoxidase system. We found a strong association of TIA-1+ cells with CD8+ cells invading the epidermis in lip and skin lesions of graft-vs-host disease in human marrow allograft recipients, as well as a sharp geographic association of TIA+ lymphocytes with CD8+ regions in human tonsil sections. Double staining of CD8 and TIA-1 antigens with fluorescein isothiocyanate and Texas red confirmed that 80% to 90% of the CD8 cells were TIA-1+ in the epidermal infiltrates. Leu-7 activity (natural killer cell) was minimal and found in only three of 17 lip biopsy specimens. These data provide new evidence that direct cytolytic attack by donor T lymphocytes is the mechanism of epithelial target cell killing in human graft-vs-host disease.
Sale
G E
GE
Department of Pathology, University of Washington, Seattle.
Anderson
P
P
Browne
M
M
Myerson
D
D
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D005260:Female; D005455:Fluorescent Antibody Technique; D006086:Graft vs Host Disease / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008046:Lip / Q000473:pathology*; D008297:Male; D012867:Skin / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
D000911:Antibodies, Monoclonal