Identification and characterization of the antigen-specific subpopulation of alloreactive CD4+ T cells in vitro and in vivo

• Published in: Transplantation Vol. 69; no. 4; pp. 605 - 609
• Main Authors: KRIEGER, N. R, FATHMAN, C. G, SHAW, M. K, RIDGWAY, W. M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 27-02-2000
• Subjects: Animals; Biological and medical sciences; CD4 antigen; CD4-Positive T-Lymphocytes - chemistry; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; Epitopes; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Immunologic Memory; Immunological tolerance; Isoantigens - immunology; Lymphocyte Activation - immunology; Lymphocyte Culture Test, Mixed; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Skin Transplantation - pathology; T-Lymphocyte Subsets - chemistry; Human; In vivo; Alloantigen; T-Lymphocyte; Homograft; Graft; Exploration; Skin; In vitro; Cell subpopulation; Biological activity; Structural analysis
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/00007890-200002270-00023

We report the identification and characterization of the small subpopulation of alloantigen-specific T cells in vitro and in vivo. This subpopulation of T cells was distinguished by up-regulation of cell surface CD4 expression. These CD4high T cells were alloantigen specific in proliferation assays in vitro, and they expressed memory/activation markers, including CD44high and CD69high. Further studies demonstrated that these allospecific CD4high cells were also present (< or = 1% of CD4+ T cells) in vivo in BALB/c (H-2d) recipients of C57BL/6 (H-2b) skin allografts. CD4high T cells isolated from regional draining lymph nodes in these skin graft recipients reacted in a donor-specific fashion to C57BL/6 splenocyte stimulator cells in mixed lymphocyte culture. Adoptive transfer of CD4high, but not CD4normal T cells, just before skin engraftment in CD4 knockout mice, reconstituted rejection. The discovery that a small subpopulation of CD4high lymph node cells contained all of the alloantigen-specific T cells may allow study of tissue-specificity and subsequent alloantigen identification in transplantation.