CD4+ regulatory T cells are spared from deletion by antilymphocyte serum, a polyclonal anti-T cell antibody.
Broad T cell depletion has been used as an integral part of treatment in transplantation and autoimmune diseases. Following depletion, residual T cells undergo homeostatic proliferation and convert to memory-like T cells. In this study, we investigated the effect of T cell depletion by antilymphocyte serum (ALS), a polyclonal anti-T cell Ab, on CD4(+) regulatory T cells. After ALS treatment, CD4(+)CD25(+) T cells underwent proliferation and expressed a memory T cell marker, CD44. One week after ALS treatment, both CD25(+) and CD25(-) T cells exhibited increased suppression of alloresponses in vitro, which waned thereafter to the levels mediated by naive CD25(+) and CD25(-) T cells. By real-time PCR analyses, ALS treatment of CD4-deficient mice adoptively transferred with Thy1.2(+)CD4(+)CD25(+)Foxp3(+) and Thy1.1(+)CD4(+)CD25(-)Foxp3(-) T cells resulted in the appearance of Thy1.2(+)CD4(+)CD25(-)Foxp3(+) and Thy1.1(+)CD4(+)CD25(+)Foxp3(+) T cells, suggesting the conversion between CD25(+) and CD25(-) T cells. Naive CD25(+) T cells expressed a higher level of intracellular Bcl-x(L) than CD25(-) T cells. Up-regulation of the Bcl-x(L) molecule during ALS-induced homeostatic expansion further promoted survival of CD25(+) and, to a lessor degree, CD25(-) cells. These results indicate that CD25(+) T cells are spared from ALS-mediated deletion, with some CD25(+) T cells converting to CD25(-) T cells, and continue to exhibit regulatory activity. The concomitant presence of T cell deletion and continuous regulatory T cell activity may underlie the therapeutic effect of ALS, particularly in treatment of autoimmune diseases.
Minamimura
Keisuke
K
Department of Surgery, Transplant Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Gao
Wenda
W
Maki
Takashi
T
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000961:Antilymphocyte Serum / Q000276:immunology*; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D000906:Antibodies; D000961:Antilymphocyte Serum; D015415:Biomarkers; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015375:Receptors, Interleukin-2; D051020:bcl-X Protein