Detection of activated T lymphocytes in the human atherosclerotic plaque.
It was recently shown that the human atherosclerotic plaque contains significant amounts of T lymphocytes, and also that smooth muscle cells in these plaques express class II MHC (Ia) antigens. These antigens are not normally present on smooth muscle cells but are inducible by interferon-gamma, a secretory product of activated T cells. Therefore, T cell activation in the plaque was analyzed by immunofluorescent detection of activation markers on T cells isolated from the plaques and in cryostat sections of carotid endarterectomy specimens. Of cells isolated from the plaque, 5% exhibited the E rosettes characteristic of T cells. One third of these cells expressed HLA-DR and VLA-1 (very late activation antigen-1), which in T cells are synthesized only in the activated state. T cells were also identified in sections using immunofluorescent detection of the T cell-specific surface protein, CD3 (Leu-4), with rhodamine labeled second-step antibodies. The frequency of activated T cells was then determined by staining the same, or serial, sections with antibodies to HLA-DR or to the interleukin-2 receptor, followed by biotin-avidin-FITC detection. Of the T cells in the plaque, 34% and 6%, respectively, expressed these cell surface proteins. Taken together, these results indicated that a substantial proportion of the T cells in atherosclerotic plaque are in an activated state. The activation pattern, with a high frequency of HLA-DR and VLA-1 expression and a much lower frequency of interleukin-2 receptor expression, was similar to that reported to occur in chronic inflammatory conditions. Interferon-gamma could be detected in and around some of the lymphocytes, suggesting that paracrine secretion of this lymphokine may occur in the plaque. T cells may be activated locally, presumably by antigen(s) presented in the context of class II MHC expressing smooth muscle cells and/or macrophages, in the atherosclerotic lesion. Such activated T cells may in turn modulate the functions of other cells in the plaque.
Hansson
G K
GK
Department of Clinical Chemistry, Gothenburg University, Sweden.
Holm
J
J
Jonasson
L
L
D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006681:HLA-D Antigens / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000032:analysis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D006681:HLA-D Antigens; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma