Characterization of T lymphocytes infiltrating human pancreas allograft affected by isletitis and recurrent diabetes.
We studied a human leukocyte antigen-identical pancreas graft transplanted into an insulin-dependent (type I) diabetic patient shortly after onset of recurrent diabetes to characterize the putative autoreactive T lymphocytes mediating the lesion. The immunohistopathological analysis revealed the presence of isletitis and a selective loss of beta-cells. The isletitis was mostly constituted by CD8+/T-lymphocyte receptor alpha,beta (TCR alpha,beta +) T lymphocytes surrounding and infiltrating the affected islets. CD4-/CD8-/TCR gamma, delta + T lymphocytes were observed within the islets. Incubation of the tissue in 15% interleukin 2 induced the migration and initial expansion of the infiltrating cells (66% CD3+ lymphocytes) for up to 2 wk; most T lymphocytes in this initial isolate were CD4+ (92% CD4+ and 7% CD8+). Long-term anti-CD3 stimulation of this T-lymphocyte population induced the selective growth of CD8+/TCR alpha,beta + (75%) and CD4-/CD8-/TCR gamma,delta + (all V1 delta +) (17%) T lymphocytes. Therefore, this strategy selectively expanded the T lymphocytes, found to be the predominantly islet-infiltrating cells, rather than the lymphocytes predominating in the initial isolate. Anti-CD3 did not stimulate growth of T lymphocytes in cultures of three isletitis-free pancreas graft biopsies. In a control experiment with a CD4(+)-rich T-lymphocyte population, long-term anti-CD3 stimulation and cloning of cytomegalovirus (CMV)-primed peripheral blood mononuclear cells from a CMV+ subject selectively induced the growth of CD4+ T-lymphocyte clones, all CMV specific.(ABSTRACT TRUNCATED AT 250 WORDS)
Santamaria
P
P
Department of Medicine, University of Minnesota, Minneapolis 55455.
Nakhleh
R E
RE
Sutherland
D E
DE
Barbosa
J J
JJ
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology / Q000601:surgery*; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D016030:Kidney Transplantation; D016035:Pancreas Transplantation / Q000276:immunology* / Q000473:pathology*; D010182:Pancreatic Diseases / Q000473:pathology; D012008:Recurrence; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D013961:Thyroid Gland / Q000276:immunology; D014184:Transplantation, Homologous
D015703:Antigens, CD; D007376:Interleukin-2