Cytotoxic folliculitis in GvHD. Evidence of follicular stem cell injury and recovery.
Recent observations indicate that stem cells of the murine hair follicle exist exclusively as a subpopulation of relatively undifferentiated outer root sheath cells located in the bulge region at the mid-portion of the follicle. Because it has been hypothesized that stem cells of interfollicular epidermis may represent targets of cytotoxic responses in acute graft-versus-host disease (AGVHD), we studied murine AGVHD and observed sequential skin biopsies for the presence and evolutionary pattern of follicular injury. Highly purified subsets of donor T cells were used to produce AGVHD to multiple minor histocompatibility (H) antigens in two strain combinations of mice matched for the major histocompatibility complex (MHC). In the C3H.SW- greater than B6 strain combination, only CD8+ effector cells produced histologic evidence in skin of AGVHD, which peaked three weeks post-transplant. In the B10.D2- greater than DBA/2 strain combination, CD4+ effector cells, and to a lesser extent, CD8+ cells, mediated disease, which peaked during the fourth week post-transplant. Analysis of skin from both strain/effector cell combinations revealed follicular infiltrates preferentially involving follicular stem cell (FSC) regions (bulge) of anagen follicles between the second and third weeks post-transplant. These infiltrates often preceded infiltration of adjacent interfollicular epidermis and were associated with follicular involution to telogen (resting) phase. By the fourth week post-transplant, greater than 50% of follicles were in telogen phase and residual inflammation was minimal. This provided a unique opportunity to observe follicular recovery from telogen.(ABSTRACT TRUNCATED AT 250 WORDS)
Murphy
G F
GF
Department of Dermatology, University of Pennsylvania, Philadelphia.
Lavker
R M
RM
Whitaker
D
D
Korngold
R
R
D000818:Animals; D005499:Folliculitis / Q000473:pathology*; D006086:Graft vs Host Disease / Q000473:pathology*; D006197:Hair / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012867:Skin / Q000276:immunology / Q000473:pathology; D013234:Stem Cells / Q000276:immunology / Q000473:pathology*