Augmentation of T cell levels and responses induced by androgen deprivation.
Androgen has been implicated as a negative regulator of host immune function and a factor contributing to the gender dimorphism of autoimmunity. Conversely, androgen deprivation has been suggested to potentiate male host immunity. Studies have shown that removal of androgen in postpubertal male mice produces an increase in size and cellularity of primary and peripheral lymphoid organs, and enhances a variety of immune responses. Yet, few details are known about the effect of androgen removal on T cell-mediated immunity. In this study, we demonstrate two pronounced and independent alterations in T cell immunity that occur in response to androgen deprivation, provided by castration, in postpubertal male mice. First, we show that levels of T cells in peripheral lymphoid tissues of mice are increased by androgen deprivation. Second, T cells from these mice transiently proliferate more vigorously to TCR- and CD28-mediated costimulation as well as to Ag-specific activation. In addition, androgen deprivation accelerates normalization of host T and B cell levels following chemotherapy-induced lymphocyte depletion. Such alterations induced by androgen deprivation may have implications for enhancing immune responses to immunotherapy and for accelerating the recovery of the immune system following chemotherapy.
Roden
Anja C
AC
Department of Urology, Comprehensive Cancer Center, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Moser
Michael T
MT
Tri
Samuel D
SD
Mercader
Maria
M
Kuntz
Susan M
SM
Dong
Haidong
H
Hurwitz
Arthur A
AA
McKean
David J
DJ
Celis
Esteban
E
Leibovich
Bradley C
BC
Allison
James P
JP
Kwon
Eugene D
ED
D000728:Androgens / Q000172:deficiency*; D000818:Animals; D018106:CD28 Antigens / Q000276:immunology; D049109:Cell Proliferation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007111:Immunity, Cellular; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009919:Orchiectomy; D009928:Organ Specificity / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D012741:Sexual Maturation / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D000728:Androgens; D018106:CD28 Antigens; D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell