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Study of Immunotherapy with Endogenous Opiod (Met-Enkephalin) Activated TILs in Fibrosarcoma Induced Balb/C Mice

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Study of Immunotherapy with Endogenous Opiod

(Met-Enkephalin) Activated Tumor In

ltrating

Lymphocytes in Fibrosarcoma Induced Balb/C Mice

Abbas Ali Amini, M.Sc.1, Jamshid Hajati, Ph.D.1, Mohammad Vodjgani, Ph.D.1,

Zahra Gheflati, B.Sc.1, Afshin Namdar, M.Sc.1, Marziyeh Holakuei, M.Sc.2,

Nematollah Khansari, Ph.D.1*

1. Immunology Department, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran 2. Immunology Department, Pasteur Institute of Iran, Tehran, Iran

* Corresponding Address: P.O.Box: 141761351, Immunology Department, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Email: nematkhansari@yahoo.com

Received: 18/Aug/2008, Accepted: 18/Mar/2009 Abstract

Objective: In this study the effects of met-enkephalin on tumor infiltrating lymphocytes for cancer treatment in fibrosarcoma bearing mice was evaluated.

Materials and Methods: Initially, to obtain the most effective dose and treating time for the inductionof CD25, splenocytes were cultured with several doses of met-enkepha-lin. Flowcytometry was used to evaluate CD25 expression. The best dose and treating time were used to stimulate tumor infiltrating lymphocytes (TILs). To obtain pure CD4+ and CD8+ cells, TILs were taken from tumors by enzymatic tissue disaggregation and purified by magnet bead cell separation. After TILs stimulation they were re-injected into three groups of other fibrosarcoma bearing mice. The first group received only CD4+ TILs, the second group received only CD8+ TILs, and the third group received both CD4+ and CD8+ TILs. A fourth group that served as the control group received only phosphate buffered saline (PBS). The effect of this treatment on tumor volume, mice survival, effector cells, regulatory T cells and serum level Bcl-2were evaluated. To analyze data in both the experimental and control groups one way ANOVA was used followed by the Tukey test. P value <0.05 was considered significant.

Results: Treatment with met-enkephalin at a dose of 10-10 M for 6 hours was most ef-fective in CD25 induction on the splenocytes of Balb/C mice. There were a significant decrease in tumors growth in both the CD8+ and CD4+ activated TILs injected groups (p<0.044 and p<0.017, respectively). The result of the CD4+ plus CD8+ activated TILs injected group was not significantly different from control group (p<0.661). There was an improvement in survival amongst the mice in all treated groups (p<0.001 for all three groups). FoxP3 levels in all groups were significantly low (p<0.001, p<0.002 and p<0.001 for the CD4+, CD8+ and CD4+ plus CD8+ activated TILs injected groups, respectively). CD25 and Bcl-2 expressions were higher in the treated groups, but only the CD4+ activated TILs injected group was significant (p<0.002 for CD25, p<0.001 for Bcl-2).

Conclusion: Met-Enk could be a potential new factor for activating lymphocytes

in vitro.

Keywords: Met-Enkephalin, Fibrosarcoma, Tumor Infiltrating Lymphocytes, Bcl-2, Treg

Yakhteh Medical Journal, Vol 11, No 4, Winter 2010, Pages: 408-417

(2)

ﻪﻣﺪﻘﻣ

ﻁﺎﺸﻧﺩﺎﺠﻳﺍﻭﻪﻓﺮﺳ،ﻝﺎﻬﺳﺍ،ﺩﺭﺩﻝﺮﺘﻨﻛﻱﺍﺮﺑﻡﻮﻴﭘﺍ،ﺶﻴﭘﺎﻫﻥﺮﻗﺯﺍ ﺪﻴﻳﻮﻟﺎﻜﻟﺁﻉﻮﻧ 20 ﺯﺍﺶﻴﺑﻱﻭﺎﺣﻡﻮﻴﭘﺍ .ﺖﺳﺍﻪﺘﻓﺮﮔﺭﺍﺮﻗﻩﺩﺎﻔﺘﺳﺍﺩﺭﻮﻣ

،ﺩﺍﺯﻥﻭﺭﺩﻱﺎﻫﺪﻴﻳﻮﻴﭘﺍ .ﺪﺷﻒﺸﻛﻪﻴﻘﺑﺯﺍﺮﺗﺩﻭﺯﻦﻴﻓﺭﻮﻣ .ﺖﺳﺍﻒﻠﺘﺨﻣ

ﻭ ﺪﻧﻮﺷﻲﻣ ﺪﻴﻟﻮﺗ ﻥﺪﺑ ﺭﺩ ﻪﻛ ﺪﻨﺘﺴﻫ ﻱﺪﻴﺘﭙﭘ ﻥﺎﻤﺘﺧﺎﺳ ﺎﺑ ﻲﺗﺎﺒﻴﻛﺮﺗ

ﺶﻘﻧ ﺕﺎﺒﻴﻛﺮﺗ ﻦﻳﺍ .ﺪﻨﺷﺎﺑﻲﻣ ﻱﺪﻴﻳﻮﻴﭘﺍ ﻱﺎﻫﻩﺪﻧﺮﻳﺬﭘ ﻲﻌﻴﺒﻃ ﺪﻧﺎﮕﻴﻟ

ﻪﺑﻲﻘﻘﺤﻣ 1975 ﻝﺎﺳﺭﺩ .ﺩﺭﺍﺩﻡﻮﻴﭘﺍﻱﺎﻫﻩﺩﺭﻭﺍﺮﻓﺯﺍﻲﺧﺮﺑﺎﺑﻲﻬﺑﺎﺸﻣ

ﺩﺮﻛﻒﺸﻛﻱﺪﻴﻳﻮﻴﭘﺍﺹﺍﻮﺧﺎﺑﺍﺭﺩﺍﺯﻥﻭﺭﺩﺭﻮﺘﻛﺎﻓﻚﻳ،ﺲﮔﻮﻫﻡﺎﻧ

ﻩﺩﺍﻮﻧﺎﺧﻭﺩ ﻥﺁﺯﺍﺲﭘ .(1) ﺪﻴﻣﺎﻧ (Enkephalin) ﻦﻴﻟﺎﻔﻜﻧﺍﺍﺭﻥﺁﻭ

ﺯﺍﻚﻳﺮﻫ .(2)ﺪﻧﺪﺷﻲﻳﺎﺳﺎﻨﺷﺰﻴﻧﺎﻫﻦﻴﻓﺭﻮﻨﻳﺩﻭﺎﻫﻦﻴﻓﻭﺭﺪﻧﺍﻲﻨﻌﻳﺮﮕﻳﺩ .ﺪﻧﺮﻴﮔﻲﻣﺎﺸﻨﻣﺍﺰﺠﻣﺯﺎﺳﺶﻴﭘﻚﻳﺯﺍ،ﺩﺍﺯﻥﻭﺭﺩﻱﺪﻴﻳﻮﻴﭘﺍﻩﺩﺍﻮﻧﺎﺧﻪﺳ

ﺯﺍ (Leucine-Enkephalinﻭ Methionin-Enkephalin) ﺎﻫﻦﻴﻟﺎﻔﻜﻧﺍ

Proopiomelanocortinﺯﺍ (ﻦﻴﻓﻭﺭﺪﻧﺍ-β) ﺎﻫﻦﻴﻓﻭﺭﺪﻧﺍ،Prepro-enkephalin

ﺯﺎﺳﺶﻴﭘﺮﻫ .ﺪﻧﻮﺷﻲﻣﻖﺘﺸﻣPreprodynorphinﺯﺍﺎﻫﻦﻴﻓﺭﻮﻧﻱﺩﻭ

ﻱﺍﺮﺑﻚﻴﺳﻼﻛﻩﺪﻧﺮﻳﺬﭘﻉﻮﻧﻪﺳ .ﺩﻮﺷﻲﻣﺪﻛﺍﺰﺠﻣﻥژﻚﻳﻪﻠﻴﺳﻭﻪﺑ

ﻭ (3) ﺪﻧﻮﺷﻲﻣﻩﺪﻴﻣﺎﻧКﻭδﻭ،μﺐﻴﺗﺮﺗﻪﺑﻪﻛﻩﺪﺷﻲﻳﺎﺳﺎﻨﺷﺎﻫﺪﻴﺋﻮﻴﭘﺍ

ﻩﺍﺮﻤﻫ

ﻪﺑ

ﻩﺪﺷ

ﻝﺎﻌﻓ

ﺭﻮﻣﻮﺗ

ﺭﺩ

ﻲﺣﺎﺸﺗﺭﺍ

ﻱﺎﻫ

ﺖﻴﺳﻮﻔﻨﻟ

ﺎﺑ

ﻰﭘﺍﺮﺗﻮﻧﻮﻤﻳﺍ

ﻲﺳﺭﺮﺑ

ﺎﻣﻮﻛﺭﺎﺳﻭﺮﺒﻴﻓ

ﻪﺑ

ﻼﺘﺒﻣ

Balb/C

ﻱﺎﻫ

ﺵﻮﻣ

ﺭﺩ

ﻦﻴﻟﺎﻔﻜﻧﺍ

-

ﺖﻣ

،1

،

M.Sc.ﺭﺍﺪﻣﺎﻧﻦﻴﺸﻓﺍ،1

،

B.Sc.ﻲﺘﻠﻔﻏﺍﺮﻫﺯ،1

،

Ph.D.ﻲﻧﺎﮕﺟﻭﺪﻤﺤﻣ،1

،

Ph.D.ﻲﺘﺟﺎﺣﺪﻴﺸﻤﺟ،1

،

M.Sc.ﻲﻨﻴﻣﺍﻲﻠﻋﺱﺎﺒﻋ

*1

،

Ph.D.ﻱﺭﺎﺴﻧﺍﻮﺧ ...ﺍﺖﻤﻌﻧ،2

،

M.Sc.ﻲﻳﻮﻛﻼﻫﻪﻴﺿﺮﻣ

ﻥﺍﺮﻳﺍ،ﻥﺍﺮﻬﺗ،ﻱژﻮﻟﻮﻧﻮﻤﻳﺍﻩﻭﺮﮔ،ﻲﻜﺷﺰﭘﻩﺪﻜﺸﻧﺍﺩ،ﻥﺍﺮﻬﺗﻲﻜﺷﺰﭘﻡﻮﻠﻋﻩﺎﮕﺸﻧﺍﺩ .1 ﻥﺍﺮﻳﺍ،ﻥﺍﺮﻬﺗ،ﻱژﻮﻟﻮﻧﻮﻤﻳﺍﻩﻭﺮﮔ،ﻥﺍﺮﻳﺍﺭﻮﺘﺳﺎﭘﻮﺘﻴﺘﺴﻧﺍ .2

ﻱژﻮﻟﻮﻧﻮﻤﻳﺍﻩﻭﺮﮔ،ﻲﻜﺷﺰﭘﻩﺪﻜﺸﻧﺍﺩ،ﻥﺍﺮﻬﺗﻲﻜﺷﺰﭘﻡﻮﻠﻋﻩﺎﮕﺸﻧﺍﺩ،141761351 :ﻲﺘﺴﭘﻕﻭﺪﻨﺻ،ﻥﺍﺮﻬﺗ،ﻥﺍﺮﻳﺍ :ﻝﻮﺌﺴﻣﻩﺪﻨﺴﻳﻮﻧﺱﺭﺩﺁ *

Email: nematkhansari@yahoo.com:ﻚﻴﻧﻭﺮﺘﻜﻟﺍﺖﺴﭘ

87/12/28 :ﻪﻟﺎﻘﻣﺵﺮﻳﺬﭘ،87/5/28 :ﻪﻟﺎﻘﻣﺖﻓﺎﻳﺭﺩ

ﻩﺪﻴﻜﭼ

ﺭﻮﻣﻮﺗﺪﺷﺭﺮﺑﻥﺁﺮﺛﺍﻭin vitroﺕﺭﻮﺻﻪﺑﻦﻴﻟﺎﻔﻜﻧﺍ -ﺖﻣﺎﺑﺭﻮﻣﻮﺗﺭﺩﻲﺣﺎﺸﺗﺭﺍﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟﻱﺯﺎﺳﻝﺎﻌﻓﺮﺛﺍﻦﻴﻴﻌﺗ :ﻑﺪﻫ *

ﻲﺑﺮﺠﺗ ﺭﺩﻲﺣﺎﺸﺗﺭﺍﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟ،ﻡﺍﻮﺗﺭﻮﻃﻪﺑﻱﺭﻮﻣﻮﺗﻱﺎﻫﺵﻮﻣ .ﺪﺷﻡﺎﺠﻧﺍﻩﺩﺎﻣBalb/Cﺵﻮﻣﻱﻭﺭﻖﻴﻘﺤﺗﻦﻳﺍ :ﺎﻫ ﺵﻭﺭ ﻭ ﺩﺍﻮﻣ *

ﺪﺷﺭﺪﻧﻭﺭ .ﺪﻧﺩﺮﻛﺖﻓﺎﻳﺭﺩCD4++CD8+ﻭ CD8CD4+ﺖﻟﺎﺣﻪﺳﺭﺩ،ﻦﻴﻟﺎﻔﻜﻧﺍ -ﺖﻣﺎﺑﻥﺪﺷﻝﺎﻌﻓﺯﺍﺪﻌﺑﺍﺭﻩﺪﺷﺺﻟﺎﺧﺭﻮﻣﻮﺗ

.ﺪﺷﻱﺮﻴﮔﻩﺯﺍﺪﻧﺍﻥﺎﻣﺭﺩﺯﺍﺪﻌﺑﻩﻭﺮﮔﺮﻫﻱﺍﺮﺑBcl-2ﺢﻄﺳﻭﻞﻣﺎﻋﻱﺎﻫﻝﻮﻠﺳﻭﻲﻤﻴﻈﻨﺗﻱﺎﻫﻝﻮﻠﺳﺢﻄﺳ،ﺎﻫﺵﻮﻣﻱﺎﻘﺑ،ﺭﻮﻣﻮﺗ

6 ﺭﺩﻥﻭﺮﻜﻴﻣ 10-10ﺯﻭﺩﺎﺑﺎﻫﺵﻮﻣ ﻲﻟﺎﺤﻃﻱﺎﻫﻝﻮﻠﺳﺢﻄﺳﺭﺩ

CD25ﻥﺎﻴﺑﺶﻳﺍﺰﻓﺍﺚﻋﺎﺑﻦﻴﻟﺎﻔﻜﻧﺍ -ﺖﻣ :ﺎﻫﻪﺘﻓﺎﻳ *

،(TIL) Tumor Infiltrating Lymphocytes ﻱﺎﻫﻩﺪﻨﻨﻛ ﺖﻓﺎﻳﺭﺩ ﻱﺎﻫﻩﻭﺮﮔ ﺭﺩ ﺭﻮﻣﻮﺗ ﺪﺷﺭ ﺖﻋﺮﺳ .ﺪﻳﺩﺮﮔ ﺖﻋﺎﺳ

ﺭﻮﻣﻮﺗﺪﺷﺭﺪﻧﻭﺭﻦﻴﻴﻌﺗﻱﺍﺮﺑ ﺮﺳ 6 ﻪﻛ ﺖﺷﺍﺩﺭﺍﺮﻗﺵﻮﻣ ﺮﺳ 12 ﻩﻭﺮﮔﺮﻫﺭﺩ) ﺖﻓﺎﻳ ﺶﻫﺎﻛﺕﺪﺷﻪﺑCD8+ ﻭ CD4+ ﻥﺎﺸﻧ ﻱﺭﺍﺩﻲﻨﻌﻣ ﻱﺎﻘﺑ ﺶﻳﺍﺰﻓﺍ ﺎﻫﻩﻭﺮﮔﻪﻤﻫ .(ﺪﻨﺘﻓﺮﮔ ﺭﺍﺮﻗﻩﺩﺎﻔﺘﺳﺍ ﺩﺭﻮﻣ ﺮﻳﺯﻱﺎﻫﺖﺴﺗﻡﺎﺠﻧﺍ ﻱﺍﺮﺑ ﺮﮕﻳﺩﺮﺳ 6 ﻭﺎﻘﺑ ﻭ

p<0/002 ،p<0/001) ﺩﻮﺑ ﺮﺘﻤﻛ ﻱﺭﺍﺩﻲﻨﻌﻣ ﺭﻮﻃ ﻪﺑ ﺎﻫﻩﻭﺮﮔ ﻪﻤﻫ ﻲﻟﺎﺤﻃ ﻱﺎﻫﻝﻮﻠﺳ ﺭﺩ FoxP3 ﺮﻛﺭﺎﻣ ﺢﻄﺳ .ﺪﻧﺩﺍﺩ

ﺭﺩBcl-2ﺢﻄﺳ .(TIL CD4++CD8+ ﻭ TIL CD8TIL CD4+ ﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻱﺎﻫﻩﻭﺮﮔﻱﺍﺮﺑ ﺐﻴﺗﺮﺗ ﻪﺑ p<0/001 ﻭ ﻭ p<0/001 ﺐﻴﺗﺮﺗ ﻪﺑ) ﺩﻮﺑ ﻝﺮﺘﻨﻛ ﻩﻭﺮﮔ ﺯﺍ ﺮﺗﻻﺎﺑ ﻱﺭﺍﺩﻲﻨﻌﻣ ﺭﻮﻃ ﻪﺑ TIL CD4++CD8+ ﻭ TIL CD4+ ﻱﺎﻫﻩﻭﺮﮔ ﺎﺑﺞﻳﺎﺘﻧ .(p<0/002) ﺩﻮﺑﻝﺮﺘﻨﻛﻩﻭﺮﮔﺯﺍﺮﺗﻻﺎﺑﻱﺭﺍﺩﻲﻨﻌﻣﺭﻮﻃﻪﺑ TIL CD4+ﻩﻭﺮﮔﺭﺩﻂﻘﻓCD25ﺮﻛﺭﺎﻣﺢﻄﺳ .(p<0/017

.ﺖﺳﺍﻩﺪﺷﻪﺘﻓﺮﮔﺮﻈﻧﺭﺩﺭﺍﺩﻲﻨﻌﻣﻪﺠﻴﺘﻧﻥﺍﻮﻨﻋﻪﺑp<0/05 .ﺪﻧﺍﻩﺪﺷﺰﻴﻟﺎﻧﺁTukeyﻥﻮﻣﺯﺁﻭOne Way ANOVA

ﻩﻮﻘﻟﺎﺑ ﺭﻮﻣﻮﺗ ﺪﺿﻞﻣﺎﻋ ﻚﻳﻥﺍﻮﻨﻋﻪﺑ ﺍﺭ ﻦﻴﻟﺎﻔﻜﻧﺍ -ﺖﻣ ﻥﺍﻮﺗﻲﻣ ﻪﻛ ﺪﻳﺁﻲﻣﺮﺑ ﻦﻴﻨﭼﻕﻮﻓﺞﻳﺎﺘﻧ ﺯﺍ :ﻱﺮﻴﮔﻪﺠﻴﺘﻧ * .ﺩﺭﻭﺁﺏﺎﺴﺣﻪﺑ

Treg،Bcl-2،ﺭﻮﻣﻮﺗﺭﺩﻲﺣﺎﺸﺗﺭﺍﺖﻴﺳﻮﻔﻨﻟ،ﺎﻣﻮﻛﺭﺎﺳﻭﺮﺒﻴﻓ،ﻦﻴﻟﺎﻔﻜﻧﺍ -ﺖﻣ:ﻥﺎﮔژﺍﻭﺪﻴﻠﻛ *

408-417 :ﺕﺎﺤﻔﺻ،88 ﻥﺎﺘﺴﻣﺯ،4 ﻩﺭﺎﻤﺷ،ﻢﻫﺩﺯﺎﻳﻝﺎﺳ،ﻪﺘﺧﺎﻳﻰﻜﺷﺰﭘﻪﻣﺎﻨﻠﺼﻓ

op3(μ)ﻭop1(δ) ،op2(К)ﺎﻳDORﻭMOR ،KORﺕﺭﻮﺻﻪﺑ

ﻞﺼﺘﻣﻱﺎﻫﻦﻴﻴﺗﻭﺮﭘﻩﺩﺍﻮﻧﺎﺧﻪﺑﻩﺪﻧﺮﻳﺬﭘﻪﺳﺮﻫ .ﺪﻧﻮﺷ ﻲﻣﻩﺩﺍﺩﻥﺎﺸﻧﺰﻴﻧ

ﻢﺘﺴﻴﺳﺮﺑﺎﻫﺪﻴﻳﻮﻴﭘﺍﺕﺍﺮﺛﺍ .ﺪﻧﺭﺍﺩﻖﻠﻌﺗ(G-Protein) GTP ﻪﺑﻩﺪﻧﻮﺷ

.ﺖﻓﺮﮔﺭﺍﺮﻗﻪﻌﻟﺎﻄﻣﺩﺭﻮﻣ 1979 ﻝﺎﺳﺭﺩﻥﺍﺮﺒﻳﻭﻂﺳﻮﺗﺭﺎﺑﻦﻴﻟﻭﺍﻲﻨﻤﻳﺍ

ﺎﺑRosetﻞﻴﻜﺸﺗﺭﺩﺍﺭTﻱﺎﻫﻝﻮﻠﺳﻲﻳﺎﻧﺍﻮﺗ،ﻦﻴﻓﺭﻮﻣﻪﻛﺖﻓﺎﻳﺭﺩﻱﻭ

ﻲﺜﻨﺧﺍﺭﺮﺛﺍﻦﻳﺍﻥﺎﺴﻛﻮﻟﺎﻧﻭﺪﻫﺩﻲﻣﺶﻫﺎﻛﺪﻨﻔﺳﻮﮔﺰﻣﺮﻗﻱﺎﻫﻝﻮﺒﻠﮔ ،ﻲﻨﻤﻳﺍﻢﺘﺴﻴﺳﺮﺑﺎﻫﺪﻴﻳﻮﻴﭘﺍﺮﻴﺛﺎﺗﺮﺑﻩﻭﻼﻋ ﻪﻌﻟﺎﻄﻣﻦﻳﺍﺭﺩ .(4) ﺪﻨﻛﻲﻣ

ﺭﺍﺮﻗﺪﻴﻳﺎﺗﺩﺭﻮﻣﺰﻴﻧﻲﻨﻤﻳﺍﻱﺎﻫﻝﻮﻠﺳﺢﻄﺳﺮﺑﻱﺪﻴﻳﻮﻴﭘﺍﻱﺎﻫﻩﺪﻧﺮﻳﺬﭘﺩﻮﺟﻭ ﻱﺎﻫﻝﻮﻠﺳﻒﻠﺘﺨﻣﻝﺎﻤﻋﺍﺮﺑﻪﻛﻲﻠﻳﺪﻌﺗﺶﻘﻧﻪﻄﺳﺍﻭﻪﺑﺎﻫﺪﻴﻳﻮﻴﭘﺍ .ﺖﻓﺮﮔ

ﻪﻛ - ﺎﻫﻥﺎﻃﺮﺳﻪﻠﻤﺟﺯﺍﻒﻠﺘﺨﻣﻱﺎﻫﻱﺭﺎﻤﻴﺑﺭﺩﺪﻨﻨﻛﻲﻣﻝﺎﻤﻋﺍﻲﻨﻤﻳﺍ

ﻱﺍﻩﮋﻳﻭﺖﻴﻤﻫﺍ - ﺪﻨﻛﻲﻣﺎﻔﻳﺍ ﺍﺭﺖﺒﻗﺍﺮﻣﺶﻘﻧﻲﻨﻤﻳﺍﻢﺘﺴﻴﺳﺎﻬﻧﺁﺭﺩ

ﺭﺩﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣ .ﺪﻧﺭﺍﺩﻲﻧﺎﻃﺮﺳﺪﺿﺹﺍﻮﺧﺎﻫﺪﻴﻳﻮﻴﭘﺍﺯﺍﻲﺧﺮﺑ .ﺪﻧﺭﺍﺩ

ﻱﺎﻣﻮﺘﺳﻼﺑﻭﺭﻮﻧﻱﺎﻫﻝﻮﻠﺳﻭﻥﺎﺴﻧﺍﺱﺍﺮﻜﻧﺎﭘﺭﻮﻣﻮﺗﺪﺷﺭ،ﺖﺸﻛﻂﻴﺤﻣ

ﻰﻨﺗﻥﻭﺭﺩﺕﺎﺸﻳﺎﻣﺯﺁﺭﺩﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣ .(6 ،5) ﺪﻨﻛﻲﻣﺭﺎﻬﻣﺍﺭﻥﺎﺴﻧﺍ

(3)

ﺭﺩﺍﺭﻥژﻭﺪﻧﺍﻱﺎﻫﺪﻴﻳﻮﻴﭘﺍﺖﻴﻟﺎﻌﻓﺎﻳﺢﻄﺳﺮﻴﻴﻐﺗﻱﺩﺪﻌﺘﻣﺕﺎﻌﻟﺎﻄﻣ .(7)

،ﻥﺍﺭﺎﻜﻤﻫﻭﺖﻴﻤﺳﺍﺵﺭﺍﺰﮔﺱﺎﺳﺍﺮﺑ .ﺪﻧﺍﻩﺩﺍﺩﻥﺎﺸﻧﺎﻫﻥﺎﻃﺮﺳﺯﺍﻲﻋﺍﻮﻧﺍ

ﻝﺎﻣﺮﻧﺮﺑﺍﺮﺑ 7 ﺎﺗﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﺢﻄﺳﺱﺍﺮﻜﻧﺎﭘﻥﺎﻃﺮﺳﻪﺑﻥﺎﻳﻼﺘﺒﻣﺭﺩ

ﺕﺎﻌﻳﺎﻣﺭﻮﻃﻦﻴﻤﻫﻭﻥﺎﺴﻧﺍﻱﺰﻐﻣﻱﺎﻫﺭﻮﻣﻮﺗﺭﺩ .(8) ﺪﺑﺎﻳﻲﻣﺶﻳﺍﺰﻓﺍ

ﺵﺭﺍﺰﮔﻥژﻭﺪﻧﺍﻱﺪﻴﻳﻮﻴﭘﺍﻱﺎﻫﺪﻴﺘﭙﭘﺶﻳﺍﺰﻓﺍﺰﻴﻧﻥﺁﻪﺑﻪﺘﺴﺑﺍﻭﻲﺘﺴﻴﻛ ﺭﺩﺰﻴﻧﺕﺎﺒﻴﻛﺮﺗﻦﻳﺍﺖﻴﻟﺎﻌﻓ،ﺎﻫﺪﻴﻳﻮﻴﭘﺍﺢﻄﺳﺮﺑﻩﻭﻼﻋ .(9)ﺖﺳﺍﻩﺪﺷ

ﺭﺩﻱﺪﻴﻠﻛﺶﻘﻧTﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟ .(10) ﺩﻮﺷﻲﻣﺮﻴﻴﻐﺗﺐﺒﺳﺎﻫﻥﺎﻃﺮﺳ

ﻲﭘﺍﺮﺗﻮﻧﻮﻤﻳﺍﻱﺍﺮﺑﺍﺭﻲﺒﺳﺎﻨﻣﺭﺍﺰﺑﺍﺎﻬﻧﺁﻭﺭﻦﻳﺍﺯﺍ .ﺪﻧﺭﺍﺩﺭﻮﻣﻮﺗﺪﺿﺮﺑﻲﻨﻤﻳﺍ

T ﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟ ،ﻝﺎﻌﻓﺮﻴﻏ ﻲﭘﺍﺮﺗﻮﻧﻮﻤﻳﺍ ﺭﺩ .ﺪﻨﻨﻛﻲﻣ ﻢﻫﺍﺮﻓ ﻥﺎﻃﺮﺳ .ﺪﻧﻮﺷﻲﻣ ﻩﺩﺍﺩﻝﺎﻘﺘﻧﺍﺭﻮﻣﻮﺗ ﻞﻣﺎﺣﻥﺎﺑﺰﻴﻣﻪﺑ ﻱﺭﻮﻣﻮﺗﺪﺿﺩﺮﻜﻠﻤﻋﺎﺑ

ﺩﺮﻜﻠﻤﻋ .ﺪﺑﺎﻳﻲﻣﻝﺎﻘﺘﻧﺍﺭﺎﻤﻴﺑﻪﺑﻩﺪﺷﻝﺎﻌﻓTﻝﻮﻠﺳﻉﻮﻧﻪﺑﻖﻓﻮﻣﻥﺎﻣﺭﺩ

ﺭﺩ ﺎﻫﻝﻮﻠﺳﻦﻳﺍﻲﻳﺎﻧﺍﻮﺗﻭ ﺭﻮﻣﻮﺗﻥﺎﻜﻣ ﻪﺑﻥﺪﻴﺳﺭﺭﺩ ﺎﻬﻧﺁﻲﻳﺎﻧﺍﻮﺗ ﻭ

.(11) ﺩﺭﺍﺩﻲﮕﺘﺴﺑﻥﺎﺑﺰﻴﻣﺭﺩﻲﻨﻤﻳﺍﺏﻮﻛﺮﺳﺎﻳﻞﻤﺤﺗﻉﻮﻧﺮﻫﺮﺑﻪﺒﻠﻏ

ﻪﻛﺪﻧﺍﻩﺩﺍﺩﻥﺎﺸﻧﻩﺪﺷﻡﺎﺠﻧﺍﻪﺘﺷﺬﮔﻱﺎﻫﻪﻫﺩﻥﺎﻴﻣﺭﺩﻪﻛﻰﻳﺎﻫﻰﺳﺭﺮﺑ

ﺪﻨﻛﺩﻭﺪﺤﻣﺍﺭﺭﻮﻣﻮﺗﺖﻓﺮﺸﻴﭘﺖﺳﺍﻦﻜﻤﻣ Tﻝﻮﻠﺳﺱﺎﺳﺍﺮﺑﻲﻨﻤﻳﺍ

ﻥﺎﺸﻧ ﻲﻧﺍﻮﻴﺣﻱﺎﻫﻝﺪﻣﺭﺩ .ﺩﺩﺮﮔﺭﻮﻣﻮﺗﺖﻓﺮﺸﻴﭘﻡﺪﻋ ﺚﻋﺎﺑﻲﺘﺣﻭ

ﺶﻨﻛﺍﻭﺭﻮﻣﻮﺗﻪﻴﻠﻋ ﻪﻛTﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟﺡﺎﺸﺗﺭﺍﻪﻛﺖﺳﺍﻩﺪﺷﻩﺩﺍﺩ

ﻉﻮﻧ .(12) ﺖﺳﺍﺯﺎﻴﻧﺩﺭﻮﻣﺭﻮﻣﻮﺗﺮﺛﻮﻣﺪﺷﺭﻡﺪﻋﻱﺍﺮﺑ،ﺪﻨﻫﺩﻲﻣﻥﺎﺸﻧ

ﻦﻜﻤﻣﺪﻧﺮﻴﮔﻲﻣﺭﺍﺮﻗﻩﺩﺎﻔﺘﺳﺍﺩﺭﻮﻣﻲﭘﺍﺮﺗﻮﻧﻮﻤﻳﺍﺭﺩﻪﻛTﻱﺎﻫﻝﻮﻠﺳ

ﺖﻳﻮﻘﺗﺍﺭﻱﺭﻮﻣﻮﺗﺪﺿﻱﺎﻫﺦﺳﺎﭘﻥﺁﻝﺎﺒﻧﺩﻪﺑﻭﻲﻨﻤﻳﺍﻱﺎﻫﺦﺳﺎﭘﺖﺳﺍ ﺕﺭﻮﺻﻪﺑﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﺮﺛﺍﻲﻠﺒﻗﺕﺎﻌﻟﺎﻄﻣﺭﺩﻪﻜﻨﻳﺍﻪﺑﻪﺟﻮﺗﺎﺑ .ﺪﻨﻳﺎﻤﻧ

ﻢﻫﺍﺭﺪﻴﻳﻮﻴﭘﺍﻦﻳﺍﻢﻴﻘﺘﺴﻣﺮﺛﺍﻱﺭﺎﻴﺴﺑﺕﺎﻌﻟﺎﻄﻣﻭﻩﺪﺷﻲﺳﺭﺮﺑin vivo

ﺕﺎﺒﺛﺍﺎﻫﺖﻴﺳﻮﻔﻨﻟﻱﻭﺭﺮﺑﻢﻫﻭ (13-16) ﻲﻧﺎﻃﺮﺳﻱﺎﻫﻝﻮﻠﺳﻱﻭﺭﺮﺑ

inﺕﺭﻮﺻﻪﺑﺎﻫﺖﻴﺳﻮﻔﻨﻟﺖﺳﺍﻩﺪﺷﻲﻌﺳﺮﺿﺎﺣﻪﻌﻟﺎﻄﻣﺭﺩ؛ﺪﻧﺍﻩﺩﻮﻤﻧ

ﺪﺷﺭﻲﻌﻴﺒﻃﺮﻴﺳﺎﺑﻞﺧﺍﺪﺗﻥﻭﺪﺑﺎﺗﺪﻧﻮﺷﻝﺎﻌﻓﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﺎﺑvitro

ﺎﺑﻪﻠﺑﺎﻘﻣﺭﺩﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﺎﺑﻩﺪﺷﻝﺎﻌﻓﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟﻲﻳﺎﻧﺍﻮﺗ،ﺭﻮﻣﻮﺗ

.ﺩﻮﺷﻩﺩﺍﺩﻥﺎﺸﻧin vivoﺕﺭﻮﺻﻪﺑﺭﻮﻣﻮﺗ

ﺎﻫ

ﺵﻭﺭ

ﺩﺍﻮﻣ

ﺵﻮﻣ ﻥﺍﺮﻳﺍﺭﻮﺘﺳﺎﭘﻮﺘﻴﺘﺴﻧﺍﺯﺍﻱﺍﻪﺘﻔﻫ 6-8 ﻦﺳﺎﺑﻩﺩﺎﻣBalb/C ﻱﺎﻫﺵﻮﻣ

ﻪﻌﻟﺎﻄﻣ،ﺪﻧﺪﻴﺳﺭﻱﺍﻪﺘﻔﻫ 12-14 ﻦﺳﻪﺑ ﺎﻫﺵﻮﻣﻲﺘﻗﻭ .ﺪﺷﻱﺭﺍﺪﻳﺮﺧ .ﺪﺷﺯﺎﻏﺁ

ﺭﻮﻣﻮﺗ

.ﺪﺷ ﻱﺭﺍﺪﻳﺮﺧﻥﺍﺮﻳﺍ ﺭﻮﺘﺳﺎﭘ ﻮﺘﻴﺘﺴﻧﺍﺯﺍ Wehi-164ﻲﻟﻮﻠﺳ ﻩﺩﺭ

ﺕﺭﻮﺻﻪﺑ 2×106 ﺮﺘﻴﻟﻭﺮﻜﻴﻣﻝﻮﻠﺳ / 100 ﺵﻮﻣﺮﻫﻪﺑﺭﻮﻣﻮﺗﺩﺎﺠﻳﺍﻱﺍﺮﺑ

ﺯﻭﺭ 9 ﻪﻛ) ﻥﺎﻣﺭﺩﻪﻠﺣﺮﻣﺯﺍﺪﻌﺑ .ﺪﺷﻖﻳﺭﺰﺗﺖﺳﺍﺭﻱﻮﻠﻬﭘﻪﺑﻱﺪﻠﺟﺮﻳﺯ

ﺮﻄﻗﻦﻳﺮﺘﺸﻴﺑﺎﻳﻝﻮﻃ .ﺪﺷﻉﻭﺮﺷﺭﻮﻣﻮﺗﺩﺎﻌﺑﺍﻱﺮﻴﮔﻩﺯﺍﺪﻧﺍ،(ﺪﺷﻡﺎﺠﻧﺍﺪﻌﺑ

ﺯﻭﺭﻚﻳﺕﺭﻮﺻﻪﺑﺲﻴﻟﻮﻛﺎﺑﺭﻮﻣﻮﺗ (W) ﺮﻄﻗﻦﻳﺮﺘﻤﻛﺎﻳﺽﺮﻋﻭ (L)

ﻢﺠﺣﺯﺍﺭﻮﻣﻮﺗﺪﺷﺭﺪﻧﻭﺭﻥﺩﺍﺩﻥﺎﺸﻧﻱﺍﺮﺑ .ﺪﺷﻱﺮﻴﮔﻩﺯﺍﺪﻧﺍﻥﺎﻴﻣﺭﺩ

TVﻭ=(Lﻭ×W

2)/2ﻝﻮﻣﺮﻓﻖﺒﻃﺭﻮﻣﻮﺗﻢﺠﺣ .ﺪﻣﺁﻞﻤﻋﻪﺑﻩﺩﺎﻔﺘﺳﺍﺭﻮﻣﻮﺗ

.(17)ﺪﻳﺩﺮﮔﻪﺒﺳﺎﺤﻣ

ﺭﻮﻣﻮﺗﻢﻀﻫ

ﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟﺪﻳﺎﺑﻪﻛﻲﻳﺎﻫﺵﻮﻣﻥﺩﺮﻛﻱﺭﻮﻣﻮﺗﺯﺍﺪﻌﺑﺯﻭﺭ 30

ﺎﺗ 1 ﺎﻫﺭﻮﻣﻮﺗﺮﺜﻛﺍﺮﻄﻗﻪﻛﻲﻄﻳﺍﺮﺷﺭﺩ،ﺪﺷﻲﻣﻪﻴﻬﺗﺎﻬﻧﺁﺯﺍﻲﺣﺎﺸﺗﺭﺍ

ﺎﺑ،ﻩﺪﺷﺝﺭﺎﺧﺎﻫﺵﻮﻣﺯﺍﻞﻳﺮﺘﺳﺍﻂﻳﺍﺮﺷﺭﺩﺎﻫﺭﻮﻣﻮﺗ،ﺩﻮﺑﺮﺘﻣ ﻲﺘﻧﺎﺳ 1/5

ﻲﻟﻮﻠﺤﻣﺭﺩﺖﻋﺎﺳ 2 ﺕﺪﻣﻪﺑﻭﻩﺪﻳﺩﺮﮔﺩﺮﺧﻚﭼﻮﻛﺕﺎﻌﻄﻗﻪﺑﻞﭙﻟﺎﻜﺳﺍ

،(ﺪﺻﺭﺩ0/025) ﺭﺎﻬﭼﻉﻮﻧ ،(ﺪﺻﺭﺩ0/025) ﻚﻳﻉﻮﻧ ﺯﺎﻧژﻼﻛ ﻱﻭﺎﺣ 37 ﺭﺩ ،(ﺎﻜﻳﺮﻣﺁ ،Sigma ﺯﺍ ﻪﺳﺮﻫ) (ﺪﺻﺭﺩ0/002) DNase I ﻭ

ﻪﺑ ﻱﺎﻫﻝﻮﻠﺳ .ﺪﻧﺪﺷ ﻩﺩﺍﺩ ﺭﺍﺮﻗ ﺪﺻﺭﺩ 5 CO2 ﻭ ﺩﺍﺮﮔﻲﺘﻧﺎﺳ ﻪﺟﺭﺩ

ﺶﻣ ﺯﺍﻭ ﻩﺪﺷﻩﺩﺍﺩﻮﺷﻭﺖﺴﺷ RPMI-1640ﺎﺑ ﺭﺎﺑﻭﺩﻩﺪﻣﺁﺖﺳﺩ

ﺎﻫﻝﻮﻠﺳﻥﺩﻮﺑﻩﺪﻧﺯﺪﺻﺭﺩﻪﻠﺣﺮﻣﻦﻳﺍﺭﺩ .ﺪﻧﺪﺷﻩﺩﺍﺩﺭﻮﺒﻋﺮﺘﻣﻭﺮﻜﻴﻣ 40 .ﺩﻮﺑﺪﺻﺭﺩ 85 ﺩﻭﺪﺣﺭﺩﻪﻛﺪﺷﻦﻴﻴﻌﺗﻮﻠﺑﻥﺎﭙﻳﺮﺗﺎﺑ

ﺪﻴﺑﺖﻨﮕﻣ

ﻭ CD4+ﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟﻱﺯﺎﺳﺺﻟﺎﺧﻱﺍﺮﺑMacs ﺖﻛﺮﺷﺪﻴﺑﺯﺍ

ﺖﻴﻔﻴﻛ ﻦﻴﻴﻌﺗﻱﺍﺮﺑ .ﺪﻣﺁﻞﻤﻋﻪﺑ ﻩﺩﺎﻔﺘﺳﺍﺭﻮﻣﻮﺗﺭﺩﻲﺣﺎﺸﺗﺭﺍCD8+

ﻖﻳﺭﺰﺗﺎﺑ .ﺪﺷﻩﺩﺎﻔﺘﺳﺍﻝﺎﺤﻃﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟﺯﺍ،Macsﺖﻴﻛ ﺩﺮﻛﺭﺎﻛ

ﺰﻣﺮﻗﻱﺎﻫﻝﻮﺒﻠﮔﻭﻪﺘﺸﮔﺩﺍﺯﺁﺎﻫﻝﻮﻠﺳ،ﻝﺎﺤﻃﻥﻭﺭﺩﻪﺑ ﺖﺸﻛﻂﻴﺤﻣ

.ﺪﻧﺪﺷﺺﻴﻠﺨﺗﺪﻴﺑﺎﺑﺎﻫﺖﻴﺳﻮﻔﻨﻟﻭ ﻩﺪﺷﺰﻴﻟﻡﻮﻴﻧﻮﻣﺁﺭﻭﺮﻠﻛﻚﻤﻛﻪﺑ

ﻚﻤﻛﻪﺑﻱﺯﺎﺳﺍﺪﺟﺯﺍﺪﻌﺑﻭﻞﺒﻗCD8ﻭCD4ﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟﺪﺻﺭﺩ

.(1 ﻞﻜﺷ) ﺩﻮﺑﺪﺻﺭﺩ 95 ﻱﻻﺎﺑﻪﻛﺪﺷﻦﻴﻴﻌﺗﺮﺘﻣﻮﺘﻳﺎﺳﻮﻠﻓ

ﻱﺎﻫﻝﻮﻠﺳ ﺹﻮﻠﺧ ،Macs ﺖﻴﻛ ﺩﺮﻛﺭﺎﻛ ﺖﻴﻔﻴﻛ ﻦﻴﻴﻌﺗ ﻱﺍﺮﺑ :1 ﻞﻜﺷ

.ﺖﻓﺮﮔﺭﺍﺮﻗﻲﺑﺎﻳﺯﺭﺍﺩﺭﻮﻣﻱﺯﺎﺳﺍﺪﺟﺯﺍﺪﻌﺑﻭﻞﺒﻗﻝﺎﺤﻃCD8ﻭ CD4

ﻭ CD4ﻱﺎﻫﺮﻛﺭﺎﻣﻱﺍﺮﺑﻝﺎﻧﻮﻠﻛﻮﻨﻣﻱﺎﻫﻱﺩﺎﺑﻲﺘﻧﺁﻚﻤﻛﻪﺑﺎﻫﺖﻴﺳﻮﻔﻨﻟ

ﻕﻮﻓﻱﺎﻫﻝﻮﻠﺳﺯﺍﻚﻳﺮﻫﺪﺻﺭﺩﺮﺘﻣﻮﺘﻳﺎﺳﻮﻠﻓﺎﺑ .ﺪﻧﺪﺷﺭﺍﺩﻥﺎﺸﻧCD8

.ﺪﺷﻦﻴﻴﻌﺗﻱﺯﺎﺳﺍﺪﺟﺯﺍﺪﻌﺑﻭﻞﺒﻗ

ﻦﻴﻟﺎﻔﻜﻧﺍ -ﺖﻣ

.ﺪﺷﻩﺩﺎﻔﺘﺳﺍ (ﺎﻜﻳﺮﻣﺁ) Sigmaﺖﻛﺮﺷﻂﺳﻮﺗﻩﺪﺷﺪﻴﻟﻮﺗﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﺯﺍ

ﻩﺪﺷﻝﺎﻌﻓﻲﺣﺎﺸﺗﺭﺍﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟﺎﺑﻲﭘﺍﺮﺗﻮﻧﻮﻤﻳﺍ

17.0%

CD8-FITC

22.6%

CD4-PE

17.0%

58.7% 22.6%

1.7%

10

103

102

101

100

100 101 102 103 104

1.6%

95.4%

CD4-PE

1.6%

58.7% 95.4%

0.4%

100 101

CD8-FITC

ﺪﻴﺑﺎﺑﻱﺯﺎﺳﺺﻟﺎﺧﺯﺍﻞﺒﻗCD8ﻭCD4ﻱﺎﻫﻝﻮﻠﺳﺪﺻﺭﺩ

(4)

ﻦﻴﻟﺎﻔﻜﻧﺍ -ﺖﻣﺎﺑﺭﺎﻤﻴﺗ ﺯﺍﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﺎﺑﺭﺎﻤﻴﺗﻪﻨﻴﻬﺑﻥﺎﻣﺯﻭﺯﻭﺩﻥﺩﺭﻭﺁﺖﺳﺩﻪﺑﻱﺍﺮﺑ

ﻥﻮﻴﺴﻧﺎﭙﺳﻮﺳ .ﺪﻣﺁﻞﻤﻋﻪﺑﻩﺩﺎﻔﺘﺳﺍﻝﺎﺤﻃﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟﻱﻭﺭ CD25ﻥﺎﻴﺑ

،ﻡﻮﻴﻧﻮﻣﺁﺭﻭﺮﻠﻛﻚﻤﻛﻪﺑﺰﻣﺮﻗﻱﺎﻫﻝﻮﺒﻠﮔﻥﺪﺷﺰﻴﻟﺯﺍﺪﻌﺑﻝﺎﺤﻃﻲﻟﻮﻠﺳ ﻱﺎﻫﺯﻭﺩﺭﻮﻀﺣﺭﺩ،(ﺪﺻﺭﺩ 5 CO2ﻭﻪﺟﺭﺩ 37) ﺖﺸﻛﻂﻴﺤﻣﺭﺩ .ﺪﻧﺪﺷﻩﺩﺍﺩﺖﺸﻛﻪﻧﺎﮔﺍﺪﺟﺭﻮﻃﻪﺑﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﻝﻮﻣ 10-11ﺎﺗ

10-5

ﺖﻋﺎﺳ 120 ﻭ 96 ،72 ،48 ،24 ،18 ،1-12 ،ﺭﺎﻤﻴﺗﺯﺍﻞﺒﻗﻱﺎﻫﻥﺎﻣﺯﺭﺩ

ﻱﺍﺮﺑﻭﻪﺘﺷﺍﺩﺮﺑ (ﻝﻮﻠﺳ 105ﺩﻭﺪﺣﺭﺩ

) ﻝﻮﻠﺳﻱﺩﺍﺪﻌﺗﻡﺍﺪﻛﺮﻫﺯﺍ،ﺭﺎﻤﻴﺗ

ﺢﻄﺳﻦﻳﺮﺗﻻﺎﺑ .ﺪﻳﺩﺮﮔﺰﻴﻟﺎﻧﺁﺮﺘﻣﻮﺘﻳﺎﺳﻮﻠﻓﺎﺑﻭﻩﺪﺷﻱﺰﻴﻣﺁﮓﻧﺭCD25

ﺪﻌﺑﻭﺪﻳﺩﺮﮔﺩﺎﺠﻳﺍﻝﻮﻣ 10-10ﺎﺑﺭﺎﻤﻴﺗﺖﻋﺎﺳ

6 ﺯﺍﺪﻌﺑCD25ﻥﺎﻴﺑ

ﻪﺑﺭﻮﻛﺬﻣﻪﻨﻴﻬﺑﺯﻭﺩﻭﻥﺎﻣﺯﺕﺪﻣ .ﺖﻓﺮﮔﺩﻮﺧﻪﺑﻲﻟﻭﺰﻧﺪﻧﻭﺭﻥﺁﺯﺍ .ﺪﺷﻩﺩﺍﺩﻢﻴﻤﻌﺗﺭﻮﻣﻮﺗﺭﺩﻲﺣﺎﺸﺗﺭﺍﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟ

ﺎﻫﺵﻮﻣﻥﺎﻣﺭﺩ ﻱﺭﻮﻣﻮﺗﺯﺍﺪﻌﺑﺯﻭﺭ 9 .ﺪﺷﻪﺘﻓﺮﮔﺮﻈﻧﺭﺩﺵﻮﻣﺮﺳ 12 ﻩﻭﺮﮔﺮﻫﻱﺍﺮﺑ

ﺮﺘﻣﻲﻠﻴﻣ 4/5-9 ﺩﻭﺪﺣﺭﺩﻱﺮﻄﻗﺎﻫﺭﻮﻣﻮﺗﻪﻛﻲﻄﻳﺍﺮﺷﺭﺩﺎﻫﺵﻮﻣﻥﺩﺮﻛ

ﻦﻳﺍﻱﺍﺮﺑ .ﺪﺷﺯﺎﻏﺁﻲﺣﺎﺸﺗﺭﺍﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟﺎﺑﺎﻫﺵﻮﻣﻥﺎﻣﺭﺩﻪﻠﺣﺮﻣ،ﺪﻨﺘﺷﺍﺩ

ﺭﻮﻣﻮﺗﻢﻀﻫﺯﺍﺪﻌﺑCD8+ﻭCD4+ﺭﻮﻣﻮﺗﺭﺩﻲﺣﺎﺸﺗﺭﺍﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟﺭﻮﻈﻨﻣ

ﻪﻧﺎﮔﺍﺪﺟCD8+ﻭCD4+ﺺﻟﺎﺧTILﺲﭙﺳﻭﻩﺪﺷﺺﻴﻠﺨﺗﺪﻴﺑﻚﻤﻛﻪﺑ

RPMI-ﺭﺩﻭﻩﺪﺷﻩﺩﺍﺩﻮﺷﻭﺖﺴﺷRPMI-1640ﺎﺑﺭﺎﺑﻭﺩ،ﻩﺪﺷﻩﺩﺍﺩﺖﺸﻛ

ﻪﺑﻭﻩﺩﺭﻭﺁﺭﺩﻥﻮﻴﺴﻧﺎﭙﺳﻮﺳﺖﻟﺎﺣﻪﺑﻝﻮﻠﺳ / ﺮﺘﻴﻟﻲﻠﻴﻣ 5×106ﺖﻈﻠﻏﺎﺑ 1640

ﻪﺑﺖﺳﺍﺭﻱﻮﻠﻬﭘﻪﺑﻱﺪﻠﺟﺮﻳﺯﺕﺭﻮﺻﻪﺑ 106ﺮﺘﻴﻟﻭﺮﻜﻴﻣﻝﻮﻠﺳ

/200 ﺵﻮﻣﺮﻫ

ﻩﻭﺮﮔﻚﻳ،CD4+ﻱﺎﻫTILﻂﻘﻓﻩﻭﺮﮔﻚﻳ؛ﺪﺷﻖﻳﺭﺰﺗﺭﻮﻣﻮﺗﻑﺍﺮﻃﺍﻪﻴﺣﺎﻧ CD8+ﻭCD4+ﻱﺎﻫTILﻥﺎﻣﺯﻢﻫﺭﻮﻃﻪﺑﻡﻮﺳﻩﻭﺮﮔﻭCD8+ﻱﺎﻫTILﻂﻘﻓ

ﺭﻮﻃﻪﺑﺍﺭCD8+ﻭCD4+ﻱﺎﻫTILﻪﻛﻲﻫﻭﺮﮔﻪﺑﻪﺘﺒﻟﺍ .ﺩﺮﻛﺖﻓﺎﻳﺭﺩﺍﺭ

2×106ﻞﻛﺭﺩﻭﻝﻮﻠﺳ

106ﺎﻫﻝﻮﻠﺳﺯﺍﻡﺍﺪﻛﺮﻫﺯﺍ،ﺩﺮﻛﻲﻣﺖﻓﺎﻳﺭﺩﻥﺎﻣﺯﻢﻫ

.ﺩﺮﻛﺖﻓﺎﻳﺭﺩPBS،ﺮﺘﻴﻟﻭﺮﻜﻴﻣ 200 ﻢﻫﻝﺮﺘﻨﻛﻩﻭﺮﮔ .ﺪﺷﻖﻳﺭﺰﺗﻝﻮﻠﺳ

ﻝﻮﻠﺳﻲﺤﻄﺳﻱﺎﻫﺮﻛﺭﺎﻣﻱﺰﻴﻣﺁﮓﻧﺭ

Anti-mouse: CD4-FITC (eBioscience), CD25- PE (eBioscience)

ﺭﺎﻤﻴﺗﺯﺍﺪﻌﺑﺯﻭﺭ 10 ﺎﻫﻩﻭﺮﮔﻪﻤﻫ،ﻱﺮﺘﻣﻮﺘﻳﺎﺳﻮﻠﻓﻱﺎﻫﺰﻴﻟﺎﻧﺁﻱﺍﺮﺑ

ﺮﺳ 6 ﻩﻭﺮﮔﺮﻫﺯﺍﻭﻢﻴﺴﻘﺗﺖﻤﺴﻗﻭﺩﻪﺑ ،ﻲﺣﺎﺸﺗﺭﺍﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟﺎﺑ

ﻥﻮﻴﺴﻧﺎﭙﺳﻮﺳ .ﺪﻨﺘﻓﺮﮔﺭﺍﺮﻗﻩﺩﺎﻔﺘﺳﺍﺩﺭﻮﻣﻲﺳﺭﺮﺑﻱﺍﺮﺑﻭﺝﺭﺎﺧﺵﻮﻣ

ﺭﺎﻤﻴﺗﺖﻤﺴﻗﺭﺩﻩﺪﺷ ﻪﺘﻔﮔﺵﻭﺭﺪﻨﻧﺎﻤﻫﺎﻫﺵﻮﻣﻲﻟﺎﺤﻃﻱﺎﻫﻝﻮﻠﺳ

105 ،ﻲﻟﺎﺤﻃﻥﻮﻴﺴﻧﺎﭙﺳﻮﺳ ﻱﺎﻫﻝﻮﻠﺳ ﺯﺍ .ﺪﺷﻪﻴﻬﺗ ﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﺎﺑ

ﻩﺩﺭﻭﺁﺭﺩ ﻥﻮﻴﺴﻧﺎﭙﺳﻮﺳ ﺖﻟﺎﺣ ﻪﺑ ﻝﻮﻠﺤﻣ ﺮﺘﻴﻟﻭﺮﻜﻴﻣ 100 ﺭﺩ ﻝﻮﻠﺳ

ﻢﻴﻧ ﺕﺪﻣ ﻪﺑ ﻭ ﻩﺩﻭﺰﻓﺍ ﺎﻬﻧﺁ ﻪﺑ ﻦﻴﻌﻣ ﺭﺍﺪﻘﻣ ﻪﺑ ﻕﻮﻓ ﻱﺎﻫﮓﻧﺭ ﺯﺍ ﻭ

ﺮﺘﻣﻮﺘﻳﺎﺳﻮﻠﻓﺎﺑﻭﺪﺷ ﻩﺩﺍﺩﻮﺷﻭﺖﺴﺷﺲﭙﺳﻭﻪﺑﻮﻜﻧﺍﺎﻣﺮﺳﺭﺩﺖﻋﺎﺳ .ﺪﻳﺩﺮﮔﺰﻴﻟﺎﻧﺁﮓﻧﺭﻭﺩﺕﺭﻮﺻﻪﺑ (Becton Dickinson)

ﻲﻟﻮﻠﺳﻥﻭﺭﺩﻱﺎﻫﺮﻛﺭﺎﻣﻱﺰﻴﻣﺁﮓﻧﺭ

(eBioscience) ﻲﺷﻮﻣTregﺖﻴﻛ .ﻒﻟﺍ

ﻲﺤﻄﺳﺮﻛﺭﺎﻣﺍﺪﺘﺑﺍ ،ﻞﻛﻮﺗﻭﺮﭘﻖﺒﻃ(FITC CD4, PE-Cy5 FoxP3)

ﺩﻭﺭﻭﻱﺍﺮﺑﻩﺪﻨﻨﻛﺍﻭﺍﺮﺗﺮﻓﺎﺑﺎﺑﺎﻫﻝﻮﻠﺳﻱﺎﺸﻏﺲﭙﺳ .ﺪﺷﻱﺰﻴﻣﺁﮓﻧﺭCD4

ﺮﻛﺭﺎﻣﺲﭙﺳ .ﺪﻳﺩﺮﮔﺖﻴﺒﺜﺗﻭﺍﻭﺍﺮﺗ،ﻝﻮﻠﺳﻥﻭﺭﺩﻪﺑFoxP3ﻱﺎﻫﻱﺩﺎﺑﻲﺘﻧﺁ

ﻢﺠﺣﺭﺩ،ﻲﻓﺎﺿﺍﮓﻧﺭﻱﻮﺷﻭﺖﺴﺷﺯﺍﺪﻌﺑ .ﺪﺷﻱﺰﻴﻣﺁﮓﻧﺭFoxP3

ﻭﻩﺩﺭﻭﺁﺭﺩﻥﻮﻴﺴﻧﺎﭙﺳﻮﺳﺖﻟﺎﺣﻪﺑ،ﻯﺮﺘﻣﻮﺘﻳﺎﺳﻮﻠﻓﻯﺰﻴﻣﺁﮓﻧﺭﺮﻓﺎﺑﺯﺍﺐﺳﺎﻨﻣ

.ﺪﺷﺰﻴﻟﺎﻧﺁﮓﻧﺭﻭﺩﺕﺭﻮﺻﻪﺑ (Becton Dickinson)ﺮﺘﻣﻮﺘﻳﺎﺳﻮﻠﻓﺎﺑ

(eBioscience) ﻭFITC Bcl-2ﺯﻮﺘﭘﻮﭘﺁﺪﺿﻦﻴﻴﺗﻭﺮﭘ .ﺏ

ﻝﺪﻣﻦﻳﺍ ﺭﺩﻲﻟﻭ ،ﺪﺷﻞﻤﻋFoxP3ﻱﺰﻴﻣﺁﮓﻧﺭﺵﻭﺭﺪﻨﻧﺎﻤﻫ Bcl-2ﺮﻛﺭﺎﻣ،FoxP3ﻱﺎﺟﻪﺑﻭﺪﺸﻧﻱﺰﻴﻣﺁﮓﻧﺭﻲﻟﻮﻠﺳﺢﻄﺳﺮﻛﺭﺎﻣ

ﻱﺍﺮﺑ ﻂﻘﻓ ﻭ ﮓﻧﺭ ﻚﺗ ﺕﺭﻮﺻﻪﺑ ﺮﻛﺭﺎﻣﻦﻳﺍ .ﺪﻳﺩﺮﮔ ﻱﺰﻴﻣﺁﮓﻧﺭ

.ﺪﺷﺰﻴﻟﺎﻧﺁBecton DickinsonﻩﺎﮕﺘﺳﺩﺎﺑﻭﻩﺪﺷﻱﺰﻴﻣﺁﮓﻧﺭBcl-2

ﻲﻜﺷﺰﭘﻡﻮﻠﻋﻩﺎﮕﺸﻧﺍﺩﻲﻜﺷﺰﭘﻩﺪﻜﺸﻧﺍﺩﻕﻼﺧﺍﻪﺘﻴﻤﻛﺭﺩﺡﺮﻃﻦﻳﺍ

.ﺖﺳﺍﻩﺪﺷﺐﻳﻮﺼﺗﻥﺍﺮﻬﺗ

ﻱﺭﺎﻣﺁﺰﻴﻟﺎﻧﺁ ﻪﺴﻳﺎﻘﻣﺖﻬﺟ .ﺪﺷﻩﺩﺎﻔﺘﺳﺍﺎﻫﻩﺩﺍﺩﺰﻴﻟﺎﻧﺁﻱﺍﺮﺑSPSSﻭwinMDI2.9ﺯﺍ

ﺯﺍ ﻦﻴﻨﭽﻤﻫﻭ TukeyﻥﻮﻣﺯﺁﻭOne Way ANOVAﺯﺍﺎﻫﻩﻭﺮﮔﻦﻴﺑ

ﻲﺣﺍﺮﻃExcelﺎﺑﺎﻫﺭﺍﺩﻮﻤﻧﺯﺍﻱﺩﺍﺪﻌﺗ .ﺪﻳﺩﺮﮔﻩﺩﺎﻔﺘﺳﺍChi-Square Tests

.ﺪﻧﺍﻩﺪﺷﻲﻘﻠﺗﺭﺍﺩﻲﻨﻌﻣﺞﻳﺎﺘﻧﻥﺍﻮﻨﻋﻪﺑp< 0/05 ﺎﺑﺞﻳﺎﺘﻧ .ﺪﻳﺩﺮﮔ

ﺎﻫ

ﻪﺘﻓﺎﻳ

ﺭﻮﻣﻮﺗﻱﺮﻴﮔﻩﺯﺍﺪﻧﺍ ﺎﺑﻩﺪﺷﻝﺎﻌﻓCD4+ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻩﻭﺮﮔ،1 ﺭﺍﺩﻮﻤﻧﻖﺑﺎﻄﻣ

ﺪﺷﺭﻩﺪﺷﻝﺎﻌﻓCD8+ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻩﻭﺮﮔﻭﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣ

ﻱﺎﻫTIﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻩﻭﺮﮔﻭﻝﺮﺘﻨﻛﻩﻭﺮﮔﻪﺑ ﺖﺒﺴﻧﻱﺮﺘﻤﻛﺭﻮﻣﻮﺗ

.ﺪﻨﺘﺷﺍﺩ،ﻥﺎﻣﺯﻢﻫﺭﻮﻃﻪﺑﻩﺪﺷﻝﺎﻌﻓCD4++CD8+

ﺭﻮﻣﻮﺗ ﺪﺷﺭﻱﻭﺭ ﻦﻴﻟﺎﻔﻜﻧﺍ -ﺖﻣﺎﺑﻩﺪﺷﻝﺎﻌﻓﻱﺎﻫTILﺮﻴﺛﺎﺗ :1 ﺭﺍﺩﻮﻤﻧ

ﺕﺭﻮﺻﻪﺑﻪﻛﺖﺷﺍﺩﺭﺍﺮﻗBalb/Cﺵﻮﻣﺮﺳ 6 ﻩﻭﺮﮔﺮﻫﺭﺩ .ﺎﻣﻮﻛﺭﺎﺳﻭﺮﺒﻴﻓ

ﺯﻭﺭﺭﺩﻭ (ﺮﻔﺻﺯﻭﺭ) ﻩﺪﺷﻱﺭﻮﻣﻮﺗWehi-164ﻝﻮﻠﺳ 2×106ﺎﺑﻱﺪﻠﺟﺮﻳﺯ

.ﺪﻧﺪﺷﻥﺎﻣﺭﺩﻦﻴﻟﺎﻔﻜﻧﺍ -ﺖﻣﺎﺑﻩﺪﺷﻝﺎﻌﻓﻱﺎﻫTILﺎﺑﻱﺪﻠﺟﺮﻳﺯﺕﺭﻮﺻﻪﺑ 9

ﻝﺎﻌﻓCD8+ TILs 106ﻡﻭﺩﻩﻭﺮﮔ،ﻩﺪﺷﻝﺎﻌﻓ CD4+ TILs 106ﻝﻭﺍﻩﻭﺮﮔ

ﻪﺘﻓﺭﻢﻫﻱﻭﺭ) TILs CD8+ 106ﻩﺍﺮﻤﻫﻪﺑ TILs CD4+ 106ﻡﻮﺳﻩﻭﺮﮔ،ﻩﺪﺷ

.ﺩﺮﻛﺖﻓﺎﻳﺭﺩPBSﻡﺭﺎﻬﭼﻩﻭﺮﮔﻭﻦﻴﻟﺎﻔﻜﻧﺍ -ﺖﻣﺎﺑﻩﺪﺷﻝﺎﻌﻓ (TILs 2×106

ﻥﺎﺸﻧ 41 ﺯﻭﺭﺎﺗﺭﺍﺩﻮﻤﻧﺭﺩﻪﻛﺪﺷﻱﺮﻴﮔﻩﺯﺍﺪﻧﺍ 53 ﺎﺗ 9 ﺯﻭﺭﺯﺍﺭﻮﻣﻮﺗﺪﺷﺭ

ﻱﺎﻫﻩﻭﺮﮔﻱﺍﺮﺑﺍﺭﺭﻮﻣﻮﺗﻢﺠﺣﺕﺍﺮﻴﻴﻐﺗﻂﺳﻮﺘﻣﺭﺍﺩﻮﻤﻧ .ﺖﺳﺍﻩﺪﺷﻩﺩﺍﺩ

.ﺖﺳﺍﻩﺪﺷﻪﺒﺳﺎﺤﻣ(L × W2)/2ﻝﻮﻣﺮﻓﺎﺑﻪﻛﺪﻫﺩﻲﻣﻥﺎﺸﻧﻒﻠﺘﺨﻣ

ﻩﺪﻨﻨﻛ ﺖﻓﺎﻳﺭﺩ ﻩﻭﺮﮔ ﻭ CD4+ ﻱﺎﻫTIL ﻩﺪﻨﻨﻛ ﺖﻓﺎﻳﺭﺩ ﻩﻭﺮﮔ

ﺪﺷﺭ ﻱﺭﺍﺩﻲﻨﻌﻣﺭﻮﻃﻪﺑﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﺎﺑﻩﺪﺷﻝﺎﻌﻓCD8+ﻱﺎﻫTIL p<0/017 ﺐﻴﺗﺮﺗﻪﺑ) ﺪﻨﺘﺷﺍﺩﻝﺮﺘﻨﻛﻩﻭﺮﮔﺎﺑﻪﺴﻳﺎﻘﻣﺭﺩﺍﺭﻱﺮﺘﻤﻛﺭﻮﻣﻮﺗ

ﺯﺍ،ﺖﺷﺍﺩﻱﺮﺘﻤﻛﺭﻮﻣﻮﺗﺪﺷﺭﻝﻭﺍﻩﻭﺮﮔﻪﻜﻨﻳﺍﻑﻼﺧﺮﺑ .(p<0/044 ﻭ

ﻩﻭﺮﮔ .(p<0/970) ﺖﺷﺍﺪﻧ ﻡﻭﺩﻩﻭﺮﮔﺎﺑ ﻲﻧﺍﺪﻨﭼﻑﻼﺘﺧﺍﻱﺭﺎﻣﺁﺮﻈﻧ

ﺖﺒﺴﻧﻥﺁﺪﺷﺭﺖﻋﺮﺳﻪﻜﻨﻳﺍﺎﺑﻩﺪﺷﻝﺎﻌﻓCD4+ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩ

ﺩﻮﺒﻧﺭﺍﺩﻲﻨﻌﻣﻲﻟﻭ،ﺩﻮﺑﺮﺘﻤﻛﻲﻬﺟﻮﺗﻞﺑﺎﻗﺭﻮﻃﻪﺑCD4++CD8+ﻩﻭﺮﮔﻪﺑ

2500.00

2000.00

1500.00

1000.00

500.00

0.00

9 15 21 27 33 41

Days

Estimated Marginal Means mm

3

Estimated Marginal of Tumor Volume

CD4++CD8+

CD8+

CD4+

Control GroupsCD4

(5)

CD4++CD8+ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻩﻭﺮﮔﻪﻜﻧﺁﺐﻟﺎﺟ .(p<0/170)

ﻲﻟﻭ،ﺖﺷﺍﺩﺶﻫﺎﻛﻝﺮﺘﻨﻛﻩﻭﺮﮔﻪﺑﺖﺒﺴﻧﻥﺁﺭﻮﻣﻮﺗﺪﺷﺭﻪﻜﻨﻳﺍﺎﺑﻩﺪﺷﻝﺎﻌﻓ ﺮﮕﻳﺩﻩﺪﺷﻥﺎﻣﺭﺩﻩﻭﺮﮔﻭﺩﺯﺍﺯﺍﺮﺘﻤﻛﺭﻮﻣﻮﺗﺪﺷﺭﺶﻫﺎﻛﺭﺎﻈﺘﻧﺍﻑﻼﺧﺮﺑ ﻑﻼﺘﺧﺍﻞﻛﺭﺩ .(p<0/661) ﺩﻮﺒﻧﺭﺍﺩﻲﻨﻌﻣﻥﺁﺭﻮﻣﻮﺗﺪﺷﺭﺶﻫﺎﻛﻭﺩﻮﺑ

ﻪﺳﺮﻫﺭﺩﻦﻤﺿﺭﺩ .(p<0/012) ﺩﻮﺑﺭﺍﺩﻲﻨﻌﻣ،ﻩﺪﺷﻥﺎﻣﺭﺩﻱﺎﻫﻩﻭﺮﮔﻦﻴﺑ .ﺪﻧﺩﺍﺩﻥﺎﺸﻧﺍﺭﺭﻮﻣﻮﺗﻞﻣﺎﻛﻞﻴﻠﺤﺗﺵﻮﻣﺮﺳ 1 ،ﻕﻮﻓﻩﺪﺷﻥﺎﻣﺭﺩﻩﻭﺮﮔ

ﺭﻮﻣﻮﺗﻪﺑﻼﺘﺒﻣﺕﺎﻧﺍﻮﻴﺣﻯﺎﻘﺑﺮﺑﻩﺪﺷﻝﺎﻤﻋﺍﻥﺎﻣﺭﺩﺮﺛﺍ ﻱﺍﺮﺑ،ﺩﻮﺒﻧﻩﺪﻨﺸﻛﻉﻮﻧﺯﺍﻪﺘﻓﺭﺭﺎﻛﻪﺑﻯﺭﻮﻣﻮﺗﻝﺪﻣﻪﻜﻨﻳﺍﻪﺑﻪﺟﻮﺗﺎﺑ

ﻯﺩﺍﺩﺭﺍﺮﻗﺭﻮﻃﻪﺑ،ﻒﻠﺘﺨﻣﻯﺎﻫﻩﻭﺮﮔﺭﺩﺎﻫﺵﻮﻣﻱﺎﻘﺑﺕﺪﻣﻲﺑﺎﻳﺯﺭﺍ

ﺮﻈﻧﺭﺩگﺮﻣﻥﺎﻣﺯﻥﺍﻮﻨﻋﻪﺑﻊﺑﺮﻣﺮﺘﻣﻲﻠﻴﻣ 400 ﻪﺑﺭﻮﻣﻮﺗﺮﻄﻗﻥﺪﻴﺳﺭ .ﺪﻳﺩﺮﮔﻡﻭﺪﻌﻣﻥﺍﻮﻴﺣﻥﺎﻣﺯﻦﻳﺍﺭﺩﻭﺪﺷﻪﺘﻓﺮﮔ

CD4+ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻩﻭﺮﮔﻪﺑﻁﻮﺑﺮﻣﺎﻘﺑﻥﺎﻣﺯﻦﻳﺮﺘﺸﻴﺑ CD8+ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻩﻭﺮﮔﻭﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﺎﺑﻩﺪﺷﻝﺎﻌﻓ

ﻩﺪﺷﻝﺎﻌﻓCD4++CD8+ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻩﻭﺮﮔ،ﺩﻮﺑﻩﺪﺷﻝﺎﻌﻓ

.(2ﺭﺍﺩﻮﻤﻧ) ﺪﻨﺘﺷﺍﺩﻝﻭﺍﻩﻭﺮﮔﻭﺩﻪﺑﺖﺒﺴﻧﻱﺮﺘﻤﻛﻱﺎﻘﺑ

ﻦﻳﺮﺧﺁ گﺮﻣ ﺯﻭﺭﻪﻛﺎﻫﺵﻮﻣ ﻥﺩﺮﻛﻱﺭﻮﻣﻮﺗ ﺯﺍﺪﻌﺑ ﺯﻭﺭ 40

ﻱﺎﻫTIﺎﺑﻩﺪﺷﻥﺎﻣﺭﺩﻩﻭﺮﮔﺭﺩ،ﺩﻮﺑ (ﻥﺎﻣﺭﺩﻥﻭﺪﺑ) ﻝﺮﺘﻨﻛﻩﻭﺮﮔﺵﻮﻣ

ﺎﺑﻩﺪﺷﻥﺎﻣﺭﺩﻩﻭﺮﮔﺭﺩﻭ (ﺪﺻﺭﺩ100) ﺎﻫﺵﻮﻣﻪﻤﻫCD8+ﻭCD4+

ﻪﺑ ﺖﺒﺴﻧﻩﻭﺮﮔﻪﺳﺮﻫﻱﺍﺮﺑ) ﺪﻧﺩﻮﺑ ﻩﺪﻧﺯ (ﺪﺻﺭﺩ67) CD4++CD8+

.(ﺩﻮﺑp> 0/001 ،ﻝﺮﺘﻨﻛﻩﻭﺮﮔ

ﺎﻫﻩﻭﺮﮔ ﻪﻤﻫ ﻱﺍﺮﺑ) ﻒﻠﺘﺨﻣ ﻱﺎﻫﻩﻭﺮﮔ ﺭﺩ ﺎﻫﺵﻮﻣ ﻱﺎﻘﺑ :2 ﺭﺍﺩﻮﻤﻧ

ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻱﺎﻫﻩﻭﺮﮔ،ﻲﻳﺍﺯﺭﻮﻣﻮﺗﺯﺍ ﺪﻌﺑﺯﻭﺭ 45 .(n=6

-ﺖﻣﺎﺑﻩﺪﺷﻝﺎﻌﻓCD8+ﻱﺎﻫTILﻭﻦﻴﻟﺎﻔﻜﻧﺍ -ﺖﻣﺎﺑﻩﺪﺷﻝﺎﻌﻓ CD4+

ﺖﻓﺎﻳﺭﺩ ﻩﻭﺮﮔ ﻪﻛﻲﻟﺎﺣ ﺭﺩ ﺪﻨﺘﺷﺍﺩ ﺪﺻﺭﺩ100 ﻱﺎﻘﺑ ﻥﺍﺰﻴﻣ ﻦﻴﻟﺎﻔﻜﻧﺍ

73 .ﺖﺷﺍﺩ ﺪﺻﺭﺩ67 ﻱﺎﻘﺑ ﻩﺪﺷ ﻝﺎﻌﻓCD4++CD8+ ﻱﺎﻫTIL ﻩﺪﻨﻨﻛ

ﺭﺩﻪﻛﺩﻮﺑ ﺪﺻﺭﺩ100 ﻥﺎﻨﭼﻢﻫﺎﻘﺑﻥﺍﺰﻴﻣﻝﻭﺍﻩﻭﺮﮔﻭﺩﺭﺩ،ﺪﻌﺑﺯﻭﺭ

ﺭﻮﻣﻮﺗ ﻩﺯﺍﺪﻧﺍ ﺎﺑ ﻲﺷﻮﻣ .ﺩﻮﺑ ﻪﺘﻓﺎﻳ ﺶﻫﺎﻛﺪﺻﺭﺩ33 ﻪﺑ ﻡﻮﺳ ﻩﻭﺮﮔ

.ﺖﺳﺍﻩﺪﺷﻪﺘﻓﺮﮔﺮﻈﻧﺭﺩﻩﺩﺮﻣ،ﻊﺑﺮﻣﺮﺘﻣﻲﻠﻴﻣ 400

ﻲﻤﻴﻈﻨﺗﻱﺎﻫﻝﻮﻠﺳCD4+FoxP3+ﻱﺎﻫﻝﻮﻠﺳ،ﻪﻌﻟﺎﻄﻣﺩﺭﻮﻣﻱﺎﻫﺵﻮﻣﻝﺎﺤﻃﺭﺩﻲﻤﻴﻈﻨﺗﻱﺎﻫﻝﻮﻠﺳﻥﺍﺰﻴﻣﻱﺮﺘﻣﻮﺘﻳﺎﺳﻮﻠﻓﺞﻳﺎﺘﻧ :2 ﻞﻜﺷ

.ﺖﺳﺍﻩﺪﺷﺰﻴﻟﺎﻧﺁﺮﺘﻣﻮﺘﻳﺎﺳﻮﻠﻓﻂﺳﻮﺗﻝﻮﻠﺳ 105ﻪﻧﻮﻤﻧﺮﻫﻱﺍﺮﺑ .ﺪﻧﺍﻩﺪﺷﺰﻴﻟﺎﻧﺁSSCFSCﺭﺩﺖﻴﺳﻮﻔﻨﻟﺖﻴﮔﺭﺩﺎﻫﻪﻧﻮﻤﻧ .ﺪﻨﺘﺴﻫ

ﻩﺪﺷﻝﺎﻌﻓﻲﺣﺎﺸﺗﺭﺍﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟﺎﺑﻲﭘﺍﺮﺗﻮﻧﻮﻤﻳﺍ

100%

80%

60%

40%

20%

0%

9 19 29 41 45 47 49 53 65 73

ﺯﻭﺭ Survival

Alive %

CD4

CD8

CD4/8

(6)

ﻪﻌﻟﺎﻄﻣﺩﺭﻮﻣﻱﺎﻫﺵﻮﻣﺭﺩTregﻱﺎﻫﻝﻮﻠﺳﻥﺍﺰﻴﻣ

ﺭﻮﻣﻮﺗﻱﺎﻘﺑﺭﺩﻲﻤﻬﻣﺶﻘﻧﻲﻤﻴﻈﻨﺗﻱﺎﻫﻝﻮﻠﺳ ﻪﻜﻨﻳﺍﻪﺑﻪﺟﻮﺗﺎﺑ

ﻪﻌﻟﺎﻄﻣ ﺩﺭﻮﻣﻱﺎﻫﻩﻭﺮﮔﺭﺩ CD4+FoxP3+ ﻱﺎﻫﻝﻮﻠﺳ ﻥﺍﺰﻴﻣ ،ﺪﻧﺭﺍﺩ

ﻩﺪﻨﻨﻛ ﺖﻓﺎﻳﺭﺩﻱﺎﻫﻩﻭﺮﮔ،3 ﺭﺍﺩﻮﻤﻧﻭ 1 ﻝﻭﺪﺟ ﻖﺑﺎﻄﻣ .ﺪﺷﻲﺳﺭﺮﺑ

ﻦﻳﺮﺗﻦﻴﻳﺎﭘﻩﺪﺷﻝﺎﻌﻓCD4++CD8+ﻱﺎﻫTILﻭﻩﺪﺷﻝﺎﻌﻓ CD4+ﻱﺎﻫTIL

ﻭ ﺪﺻﺭﺩ6/6 ± 0/29 ﺐﻴﺗﺮﺗ ﻪﺑ) ﺪﻨﺘﺷﺍﺩ ﺍﺭ FoxP3 ﺭﻮﺘﻛﺎﻓ ﺢﻄﺳ

ﻱﺭﺍﺩﻲﻨﻌﻣﺭﻮﻃﻪﺑﻩﺪﺷﻥﺎﻣﺭﺩﻱﺎﻫﻩﻭﺮﮔﻪﻤﻫﻞﻛﺭﺩ .(6/59 ± 0/23

ﻩﻭﺮﮔ ﻱﺍﺮﺑ ) ﺪﻨﺘﺷﺍﺩ ﻝﺮﺘﻨﻛ ﻩﻭﺮﮔ ﻪﺑ ﺖﺒﺴﻧ ﻱﺮﺘﻤﻛ FoxP3 ﺢﻄﺳ

P-valueﺭﺎﻴﻌﻣﻑﺍﺮﺤﻧﺍﻩﺍﺮﻤﻫﻪﺑﻒﻠﺘﺨﻣﻱﺎﻫﻩﻭﺮﮔﺭﺩBcl-2FoxP3 ،CD25ﺪﺻﺭﺩ :1 ﻝﻭﺪﺟ

ﺎﻫﻩﻭﺮﮔ

FoxP3 CD25

Bcl-2

FoxP3 ﺪﺻﺭﺩ

ﺭﺎﻴﻌﻣﻑﺍﺮﺤﻧﺍ ±

P. Value CD25 ﺪﺻﺭﺩ

ﺭﺎﻴﻌﻣﻑﺍﺮﺤﻧﺍ ±

P. Value Bcl-2 ﺪﺻﺭﺩ

ﺭﺎﻴﻌﻣﻑﺍﺮﺤﻧﺍ ±

P. Value

CD4+ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻩﻭﺮﮔ

6/60 ± 0/29

p < 0/001

29/92 ± 1/82

p < 0/002

48/87 ± 6/71

p < 0/001

CD8+ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻩﻭﺮﮔ

6/89 ± 0/32

p < 0/002

27/52 ± 1/33

p < 0/175

38/97 ± 4/14

p < 0/952

CD8++CD4+ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻩﻭﺮﮔ

6/59 ± 0/23

p < 0/001

26/64 ± 0/57

p < 0/554

45/57 ± 1/92

p < 0/017

ﻝﺮﺘﻨﻛﻩﻭﺮﮔ

7/49 ± 0/01

p < 1/000

25/19 ± 2/96

p < 1/000

37/73 ± 0/85

p < 1/000

.ﺖﺳﺍﻩﺪﺷﻪﺘﻓﺮﮔﺮﻈﻧﺭﺩﺪﺻﺭﺩ 1 ﻲﻔﻨﻣﻝﺮﺘﻨﻛ .ﻒﻠﺘﺨﻣﻱﺎﻫﻩﻭﺮﮔﺭﺩBcl-2ﺢﻄﺳﻡﺍﺮﮔﻮﺘﺴﻴﻫﺭﺍﺩﻮﻤﻧ :3 ﻞﻜﺷ

ﻚﺗﺕﺭﻮﺻﻪﺑﻲﻟﺎﺤﻃﻝﻮﻠﺳ 104ﻪﻧﻮﻤﻧﺮﻫﻱﺍﺮﺑ .ﺪﻧﺍﻩﺪﺷﺰﻴﻟﺎﻧﺁ SSCFSCﺭﺩﺖﻴﺳﻮﻔﻨﻟﺖﻴﮔﺭﺩﺎﻫﻪﻧﻮﻤﻧ

(7)

ﻭCD4

++CD8+ﻩﻭﺮﮔﻭp<0/002

ﻭ CD8

+ﻩﻭﺮﮔ،CD4+

ﻭp<0/001

ﺩﻮﺟﻭﻱﺭﺍﺩﻲﻨﻌﻣﻑﻼﺘﺧﺍﻩﺪﺷﻥﺎﻣﺭﺩﻩﻭﺮﮔﻪﺳﻦﻴﺑﻲﻟﻭ،(p<0/001 .ﺩﻮﺑﺪﺻﺭﺩ0/29 ﻕﻮﻓﺖﺴﺗﻲﻔﻨﻣﻝﺮﺘﻨﻛ .ﺖﺷﺍﺪﻧ

ﺖﺴﺗﺕﻼﭘﺕﺍﺩﺯﺍﻪﻧﻮﻤﻧﻚﻳ،ﺎﻫﻩﻭﺮﮔﺯﺍﻚﻳﺮﻫﺯﺍ 2 ﻞﻜﺷﺭﺩ

YﺭﻮﺤﻣﻭCD4-FITCﻪﺑﻁﻮﺑﺮﻣXﺭﻮﺤﻣ .ﺖﺳﺍﻩﺪﺷﻩﺩﺍﺩﻥﺎﺸﻧﻕﻮﻓ .ﺪﺷﺎﺑﻲﻣFoxP3-PE-Cy5ﻪﺑﻁﻮﺑﺮﻣ

7.00

6.00

5.00

4.00

CD4 CD8 CD4/8 Control

ﺎﻫﻩﻭﺮﮔ

CD+FoxP3+

(n=6 ﺎﻫﻩﻭﺮﮔﻪﻤﻫﻱﺍﺮﺑ) CD4+ﻲﻟﺎﺤﻃﻱﺎﻫﻝﻮﻠﺳﺭﺩ FoxP3ﺢﻄﺳ :3 ﺭﺍﺩﻮﻤﻧ

CD25ﺮﻛﺭﺎﻣ

ﻱﺎﻫTIL ﻩﺪﻨﻨﻛ ﺖﻓﺎﻳﺭﺩ ﻩﻭﺮﮔ ﺭﺩ ﻂﻘﻓ CD25 ﺮﻛﺭﺎﻣ ﺢﻄﺳ

ﺩﻮﺑ ﻝﺮﺘﻨﻛ ﻩﻭﺮﮔ ﺯﺍ ﺮﺗﻻﺎﺑ ﻱﺭﺍﺩﻲﻨﻌﻣ ﺭﻮﻃ ﻪﺑ ﻩﺪﺷﻝﺎﻌﻓ CD4+

ﺮﻳﺎﺳ ﺯﺍ ﻕﻮﻓﻩﻭﺮﮔ ﺭﺩﺮﻛﺭﺎﻣﻦﻳﺍ ﺢﻄﺳ .(1 ﻝﻭﺪﺟ) (p<0/002) 1/33 ﺎﺑﻪﺴﻳﺎﻘﻣﺭﺩ 29/92 ± 1/82)ﺩﻮﺑﺮﺗﻻﺎﺑﺰﻴﻧﻲﻧﺎﻣﺭﺩﻱﺎﻫﻩﻭﺮﮔ

ﻩﻭﺮﮔ 26/64 ± 0/57 ﻭﻩﺪﺷﻝﺎﻌﻓCD8+ﻱﺎﻫTILﻩﻭﺮﮔ 27/52 ±

ﻩﻭﺮﮔ ﻪﺑﺖﺒﺴﻧﻑﻼﺘﺧﺍﻦﻳﺍ ﻭ (ﻩﺪﺷﻝﺎﻌﻓ CD4++CD8+ﻱﺎﻫTIL

ﺭﺩ .(p<0/029) ﺩﻮﺑ ﺭﺍﺩﻲﻨﻌﻣ ﻩﺪﺷﻝﺎﻌﻓ CD4++CD8+ ﻱﺎﻫTIL

CD4++CD8+ﻱﺎﻫTILCD8+ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻱﺎﻫﻩﻭﺮﮔ

ﺐﻴﺗﺮﺗ ﻪﺑ) ﺩﻮﺒﻧ ﺭﺍﺩﻲﻨﻌﻣ ﻕﻮﻓ ﺮﻛﺭﺎﻣ ﺶﻳﺍﺰﻓﺍ ﻥﺍﺰﻴﻣ ،ﻩﺪﺷ ﻝﺎﻌﻓ

.(4ﺭﺍﺩﻮﻤﻧ)(p<0/554 ﻭp<0/0175

35.00

30.00

25.00

20.00

CD4 CD8 CD4/8 Control

ﺎﻫﻩﻭﺮﮔ

CD4+CD25+

ﺩﺭﻮﻣﻱﺎﻫﻩﻭﺮﮔﻲﻟﺎﺤﻃﻱﺎﻫﻝﻮﻠﺳﺭﺩCD4+CD25+ﺢﻄﺳ :4 ﺭﺍﺩﻮﻤﻧ

(n=6 ﺎﻫﻩﻭﺮﮔﻪﻤﻫﻱﺍﺮﺑ) ﻪﻌﻟﺎﻄﻣ

55.00

50.00

45.00

40.00

35.00

30.00

CD4 CD8 CD4/8 Control

ﺎﻫﻩﻭﺮﮔ

Bcl.2%

ﻪﻌﻟﺎﻄﻣﺩﺭﻮﻣﻱﺎﻫﻩﻭﺮﮔﻲﻟﺎﺤﻃﻱﺎﻫﻝﻮﻠﺳﺭﺩBcl-2ﺢﻄﺳ :5 ﺭﺍﺩﻮﻤﻧ

(n=6 ﺎﻫﻩﻭﺮﮔﻪﻤﻫﻱﺍﺮﺑ)

Bcl-2ﺮﻛﺭﺎﻣ

ﺩﺭﻮﻣ ﻱﺎﻫﻩﻭﺮﮔﻲﻟﺎﺤﻃ ﻱﺎﻫﻝﻮﻠﺳ ﺯﺍ ،Bcl-2 ﺢﻄﺳ ﻦﻴﻴﻌﺗ ﻱﺍﺮﺑ

ﺖﻓﺎﻳﺭﺩ ﻩﻭﺮﮔ ﻪﺑ ﻁﻮﺑﺮﻣ Bcl-2 ﺢﻄﺳ ﻦﻳﺮﺗﻻﺎﺑ .ﺪﺷ ﻩﺩﺎﻔﺘﺳﺍ ﻪﻌﻟﺎﻄﻣ

ﻦﻳﺮﺗﻦﻴﻳﺎﭘﻭ (ﺪﺻﺭﺩ48/87 ± 6/71) ﻩﺪﺷﻝﺎﻌﻓCD4+ﻱﺎﻫTILﻩﺪﻨﻨﻛ

± 4/14) ﻩﺪﺷﻝﺎﻌﻓCD8+ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻩﻭﺮﮔﻪﺑﻁﻮﺑﺮﻣﻥﺁ

ﺭﺩﺭﻮﺑﺰﻣﺭﻮﺘﻛﺎﻓﺢﻄﺳ 1 ﻝﻭﺪﺟﻭ 5 ﺭﺍﺩﻮﻤﻧﻖﺑﺎﻄﻣ .ﺩﻮﺑ (ﺪﺻﺭﺩ38/97

CD4++CD8+ﻭﻩﺪﺷﻝﺎﻌﻓCD4+ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻱﺎﻫﻩﻭﺮﮔ

ﻱﺍﺮﺑp<0/001) ﺩﻮﺑﻝﺮﺘﻨﻛﻩﻭﺮﮔﺯﺍﺮﺗﻻﺎﺑﻱﺭﺍﺩﻲﻨﻌﻣﺭﻮﻃﻪﺑﻩﺪﺷﻝﺎﻌﻓ .(CD4++CD8+ﻩﻭﺮﮔﻱﺍﺮﺑp<0/017 CD4+ﻩﻭﺮﮔ

ﻝﺎﻌﻓCD8+ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻩﻭﺮﮔﺭﺩﺭﻮﺑﺰﻣﺭﻮﺘﻛﺎﻓﺢﻄﺳ

ﻑﻼﺘﺧﺍ .(p<0/952) ﺖﺷﺍﺪﻧﻝﺮﺘﻨﻛﻩﻭﺮﮔﺎﺑﻱﺭﺍﺩﻲﻨﻌﻣﺕﻭﺎﻔﺗﻩﺪﺷ

ﺰﻴﻧ ﻩﺪﺷﻝﺎﻌﻓCD8+ﻱﺎﻫTILﻩﺪﻨﻨﻛ ﺖﻓﺎﻳﺭﺩﻩﻭﺮﮔﺎﺑﻕﻮﻓﻩﻭﺮﮔﻭﺩ

ﻚﻳﺮﻫﺯﺍ،3 ﻞﻜﺷﺭﺩ .(p<0/050 ﻭp<0/002 ﺐﻴﺗﺮﺗﻪﺑ) ﺩﻮﺑﺭﺍﺩﻲﻨﻌﻣ .ﺖﺳﺍﻩﺪﺷﻩﺩﺭﻭﺁﻡﺍﺮﮔﻮﺘﺴﻴﻫﺕﺭﻮﺻﻪﺑﻪﻧﻮﻤﻧﻚﻳﺎﻫﻩﻭﺮﮔﺯﺍ

ﺚﺤﺑ

ﻱﺭﻮﻣﻮﺗﺪﺿﺦﺳﺎﭘﺭﺩﻞﻣﺎﻋﻱﺎﻫﻝﻮﻠﺳﻦﻳﺮﺗﻢﻬﻣTﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟ

ﺖﻬﺟ ﻪﻛ ﻲﻳﺎﻫﺵﻼﺗ ﻩﺪﻤﻋ ﺖﻤﺴﻗ ﻊﻗﺍﻭ ﺭﺩ .ﺪﻧﻮﺷﻲﻣ ﺏﻮﺴﺤﻣ

ﻦﻳﺍ ﻲﻳﺍﺭﺎﻛ ﻭ ﻲﻳﺎﻧﺍﻮﺗ ﺶﻳﺍﺰﻓﺍ ﻱﺍﺮﺑ ،ﺩﺮﻴﮔﻲﻣ ﻡﺎﺠﻧﺍ ﻲﭘﺍﺮﺗﻮﻧﻮﻤﻳﺍ

ﻲﻳﺎﻫﺵﻭﺭﻪﻠﻤﺟﺯﺍ .ﺪﺷﺎﺑﻲﻣﻱﺭﻮﻣﻮﺗﻱﺎﻫﻝﻮﻠﺳﺎﺑﻪﻠﺑﺎﻘﻣﻱﺍﺮﺑﺎﻫﻝﻮﻠﺳ

،ﺖﺳﺍﻪﺘﻓﺮﮔﺭﺍﺮﻗﻩﺩﺎﻔﺘﺳﺍﺩﺭﻮﻣﺎﻫﻝﻮﻠﺳﻦﻳﺍﻲﻳﺍﺭﺎﻛﺶﻳﺍﺰﻓﺍﻱﺍﺮﺑﻪﻛ ،ﻒﻠﺘﺨﻣﻱﺎﻫﻦﻳﺎﻛﻮﺘﻳﺎﺳﺪﻨﻧﺎﻣﻥﻮﮔﺎﻧﻮﮔﺕﺎﺒﻴﻛﺮﺗﺯﺍﻩﺩﺎﻔﺘﺳﺍﻪﺑﻥﺍﻮﺗﻲﻣ

Tﻱﺎﻬﻟﻮﻠﺳﻚﻴﺘﻧژﻲﺳﺪﻨﻬﻣﻭﻲﻧﺎﻣﺭﺩﻮﺗﺮﭘ،ﻲﻧﺎﻣﺭﺩﻲﻤﻴﺷﺎﺑﻲﻫﺍﺮﻤﻫ

ﻡﺎﻧﻪﺑ ،ﺩﺍﺯﻥﻭﺭﺩ ﺪﻴﻳﻮﻴﭘﺍﻚﻳﺯﺍﻪﻌﻟﺎﻄﻣ ﻦﻳﺍﺭﺩ .(23-18)ﺩﺮﻛﻩﺭﺎﺷﺍ .ﺪﺷﻩﺩﺎﻔﺘﺳﺍTﻱﺎﻫﻝﻮﻠﺳﻲﻳﺎﻧﺍﻮﺗﺶﻳﺍﺰﻓﺍﻱﺍﺮﺑﻦﻴﻟﺎﻔﻜﻧﺍ -ﺖﻣ

ﺮﺑﺍﺮﺑ ﺭﺩ ﺐﻟﺎﻏ ﻲﺻﺎﺼﺘﺧﺍ ﻲﻨﻤﻳﺍ ﺦﺳﺎﭘ ﻪﻛ ﻲﻳﺎﺟ ﻥﺁ ﺯﺍ

ﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟﻪﻄﺳﺍﻭﺎﺑﺎﻫﻥﺎﻃﺮﺳﻭﻲﻟﻮﻠﺳﻞﺧﺍﺩﻱﺎﻫﻢﺴﻴﻧﺎﮔﺭﺍﻭﺮﻜﻴﻣ ،(23) ﺩﺮﻳﺬﭘﻲﻣ ﺕﺭﻮﺻ ﻚﻴﺴﻛﻮﺗﻮﺘﻳﺎﺳ T ﻱﺎﻫﻝﻮﻠﺳ ﻭ TH1

ﻩﺪﻧﺮﻳﺬﭘ .ﺪﻨﺘﻓﺮﮔ ﺭﺍﺮﻗ ﻩﺩﺎﻔﺘﺳﺍ ﺩﺭﻮﻣ ﻭ ﺺﻴﻠﺨﺗ ﺎﻫﻝﻮﻠﺳ ﻦﻳﺍ

ﺮﺜﻛﺍ ﺭﺩTIL ﻱﺎﻫﻝﻮﻠﺳ ﺯﺍ ﻲﻤﻛ ﺪﺻﺭﺩ ﻱﻭﺭ ﻪﻛ(CD25)ﻭ IL-2

ﻚﻳﺮﺤﺗ ﻪﺠﻴﺘﻧ ﻥﺍﻮﻨﻋ ﻪﺑ ،(24-26) ﺩﻮﺷﻲﻣ ﻥﺎﻴﺑ ﺎﻫﺭﻮﻣﻮﺗ ﻉﺍﻮﻧﺍ

ﻪﺟﻮﺗﺎﺑ ﻭﺭﻦﻳﺍﺯﺍ .(28 ،27) ﺩﻮﺷﻲﻣﻪﺘﻓﺮﮔﺮﻈﻧﺭﺩﺮﻴﺧﺍﻲﻧژﻲﺘﻧﺁ

(8)

،(29 ،3) ﻲﻨﻤﻳﺍ ﻢﺘﺴﻴﺳﻥﺩﺮﻛ ﻝﺎﻌﻓ ﺭﺩﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﻲﻳﺎﻧﺍﻮﺗ ﻪﺑ

ﺎﻫﺖﻴﺳﻮﻔﻨﻟ ﻥﺪﺷﻝﺎﻌﻓ ﻲﺑﺎﻳﺯﺭﺍ ﻱﺍﺮﺑ ﻱﺮﻛﺭﺎﻣ ﻥﺍﻮﻨﻋ ﻪﺑCD25 ﺯﺍ

ﻪﻌﻟﺎﻄﻣﻦﻳﺍﺭﺩ .ﺪﻣﺁﻞﻤﻋﻪﺑﻩﺩﺎﻔﺘﺳﺍﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﺎﺑﺭﺎﻤﻴﺗﺯﺍﺪﻌﺑ

ﺐﺟﻮﻣﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﺎﺑ Tﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟﺭﺎﻤﻴﺗ ﻪﻛﺪﺷﻩﺩﺍﺩﻥﺎﺸﻧ

ﻱﺭﻮﻣﻮﺗﻱﺎﻫﻝﻮﻠﺳ .ﺩﺩﺮﮔﻲﻣﺎﻫﻝﻮﻠﺳﻦﻳﺍﺭﺩ CD25 ﻥﺎﻴﺑﺶﻳﺍﺰﻓﺍ

ﺢﺷﺮﺗﻭ ﺪﻴﻟﻮﺗﺎﺑ ﻭ ﺪﻧﺭﺍﺬﮔﻲﻣ ﺮﻴﺛﺎﺗﻲﻨﻤﻳﺍﻢﺘﺴﻴﺳﺖﻴﻟﺎﻌﻓﻱﻭﺭ ﺰﻴﻧ

ﻲﻜﻳ .ﺪﻨﻨﻛﻲﻣ ﺖﻣﻭﺎﻘﻣ ﻲﻨﻤﻳﺍ ﻢﺘﺴﻴﺳ ﻞﺑﺎﻘﻣ ﺭﺩ ﺎﻫﺭﻮﺘﻛﺎﻓ ﻉﺍﻮﻧﺍ

ﺭﺩ ﺯﻮﺘﭘﺎﭘﺁ ﻱﺎﻘﻟﺍ ،ﻲﻨﻤﻳﺍ ﻢﺘﺴﻴﺳ ﻪﺑ ﺭﻮﻣﻮﺗ ﻪﻠﻤﺣ ﻱﺎﻫﻢﺴﻴﻧﺎﻜﻣ ﺯﺍ

ﻥﺎﺸﻧﻪﻜﻨﻳﺍ ﻪﺑ ﻪﺟﻮﺗ ﺎﺑ .(30-35) ﺪﺷﺎﺑﻲﻣ ﻲﺣﺎﺸﺗﺭﺍ ﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟ

ﻱﺍﺮﺑ ﻪﻛ ﻲﻳﺎﻫﺖﻴﺳﻮﻔﻨﻟ ﺭﺩBcl-2 ﺢﻄﺳ ﻥﺩﻮﺑ ﻻﺎﺑ ﻪﻛ ﻩﺪﺷ ﻩﺩﺍﺩ

ﺢﻄﺳ ،ﺩﺭﺍﺩﻱﺮﺘﻬﺑ ﺞﻳﺎﺘﻧﺪﻧﺮﻴﮔﻲﻣﺭﺍﺮﻗ ﻩﺩﺎﻔﺘﺳﺍﺩﺭﻮﻣ ﻲﭘﺍﺮﺗﻮﻧﻮﻤﻳﺍ ﻱﺭﺎﻬﻣﻭﻲﺘﻳﻮﻘﺗﻱﺎﻫﻭﺮﻴﻧﺪﻨﻳﺍﺮﺑﻪﺠﻴﺘﻧﻪﻛﻲﻠﻣﺎﻋﻥﺍﻮﻨﻋﻪﺑﻕﻮﻓﺮﻛﺭﺎﻣ ﻩﻭﺮﮔﺭﺩBcl-2ﺢﻄﺳ ﻦﻳﺮﺗﻻﺎﺑ .ﺪﺷﻱﺮﻴﮔﻩﺯﺍﺪﻧﺍ،ﺪﻫﺩﻲﻣﻥﺎﺸﻧﺍﺭ

ﻪﻛﻩﺩﻮﺑﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﺎﺑﻩﺪﺷﻝﺎﻌﻓCD4+ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩ

ﻻﺎﻤﺘﺣﺍﺩﺍﺩﻲﻣﻥﺎﺸﻧﺮﻣﺍﻦﻳﺍ .ﺖﺷﺍﺩﻖﺑﺎﻄﺗCD25ﺢﻄﺳﻥﺩﻮﺑﻻﺎﺑﺎﺑ

ﻒﻳﺎﻇﻭﻝﺎﻤﻋﺍ ﺭﺩﺮﺘﺸﻴﺑﻲﻳﺎﻧﺍﻮﺗﺮﺑﻩﻭﻼﻋ ﻕﻮﻓﻩﻭﺮﮔ ﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟ

ﻲﺘﻗﻭﻕﻮﻓﻱﺎﻫ ﻪﺘﻓﺎﻳ .ﺪﻨﺘﺴﻫﻡﻭﺎﻘﻣﺰﻴﻧﺯﻮﺘﭘﺎﭘﺁﻞﺑﺎﻘﻣ ﺭﺩ،ﻱﺩﺮﻜﻠﻤﻋ

،ﺪﻧﻮﺷﻞﻴﻠﺤﺗﻩﺪﺷﻥﺎﻣﺭﺩﻱﺎﻫﻩﻭﺮﮔ ﺭﺩﺭﻮﻣﻮﺗ ﺪﺷﺭﺪﻧﻭﺭﺭﺎﻨﻛﺭﺩ

ﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻩﻭﺮﮔ .ﺪﻨﻛﻲﻣﻪﺟﻮﺗﺐﻠﺟﺮﺘﺸﻴﺑﻩﺪﻣﺁﺖﺳﺩﻪﺑﻪﺠﻴﺘﻧ

Bcl-2 ﺢﻄﺳ ﻪﻜﻨﻳﺍ ﻑﻼﺧ ﺮﺑ ﻩﺪﺷ ﻝﺎﻌﻓ CD4++CD8+ ﻱﺎﻫTIL

ﻥﺎﻣﺭﺩﻱﺎﻫﻩﻭﺮﮔﻦﻴﺑ ﺭﺩﺍﺭ CD25 ﺢﻄﺳﻦﻳﺮﺗﻦﻴﻳﺎﭘ،ﺖﺷﺍﺩﻲﻳﻻﺎﺑ

ﻱﺎﻫﻝﻮﻠﺳﺩﺍﺪﻌﺗ ﻻﺎﻤﺘﺣﺍﻪﻛ ﺖﺳﺍﻪﺘﻜﻧ ﻦﻳﺍﺮﮕﻧﺎﻴﺑ .ﺩﺍﺩ ﻥﺎﺸﻧﻩﺪﺷ

ﻲﻳﺍﺭﺎﻛ ﻩﺪﺷ ﺐﺟﻮﻣ ﻦﻳﺍﺮﺑﺎﻨﺑ ،ﺪﺷﺎﺑﻲﻣ ﻦﻴﻳﺎﭘ ﻩﻭﺮﮔ ﻦﻳﺍ ﺭﺩ ﻞﻣﺎﻋ

.ﺪﺷﺎﺑﺮﺗﻒﻴﻌﺿﺎﻫﻩﻭﺮﮔﺮﻳﺎﺳﻪﺑﺖﺒﺴﻧﺭﻮﻣﻮﺗﻞﻴﻠﺤﺗﺭﺩﺎﻫﻝﻮﻠﺳ

ﻭ T ،HLA-DRﻱﺎﻫﻝﻮﻠﺳﺖﻴﻟﺎﻌﻓ ﻱﺎﻫﺮﻛﺭﺎﻣﻥﺎﻴﻣﺭﺩ ﺮﻫﺎﻇﻪﺑ

(26 ،25) ﺪﻧﺭﺍﺪﻧﻲﻧﺍﻮﺧﻢﻫﺎﻫTILﻥﺩﻮﺑﻝﺎﻌﻓﻲﻌﻗﺍﻭﻂﻳﺍﺮﺷﺎﺑCD69

ﻥﺪﺷﻝﺎﻌﻓﺯﺍﺪﻌﺑﺎﻫﺮﻛﺭﺎﻣﻦﻳﺍﻪﻛﺪﺷﺎﺑﻞﻴﻟﺩﻦﻳﺍﻪﺑﺖﺳﺍﻦﻜﻤﻣﻪﻛ

ﺖﻴﻌﻤﺟﻱﻭﺭ ﻪﻛCD25 ﻞﺑﺎﻘﻣﺭﺩ .ﺪﻧﻮﺷﻲﻣﻥﺎﻴﺑﻲﻧﻻﻮﻃ ﺕﺪﻣﻪﺑ

ﻥﺍﻮﻨﻋﻪﺑ ،ﺩﻮﺷﻲﻣ ﻥﺎﻴﺑﺎﻫﺭﻮﻣﻮﺗ ﻉﺍﻮﻧﺍ ﺮﺘﺸﻴﺑﺭﺩ ﺎﻫTIL ﺯﺍ ﻲﻜﭼﻮﻛ

ﺭﺩﻲﻤﻬﻣﺶﻘﻧﻥﺎﻣﺯﻢﻫﻭﺩﻮﺷﻲﻣﻪﺘﻓﺮﮔﺮﻈﻧﺭﺩﺮﻴﺧﺍﻚﻳﺮﺤﺗﻪﺠﻴﺘﻧ

ﻲﺑﺎﻳﺯﺭﺍﻱﺍﺮﺑﻪﻛﺪﻨﻛﻲﻣﺎﻔﻳﺍﺎﻬﻧﺁﺩﺮﻜﻠﻤﻋﻭTﻱﺎﻫﻝﻮﻠﺳﺮﻴﺜﻜﺗﻢﻴﻈﻨﺗ

،27) ﺖﺳﺍﻪﺘﻓﺮﮔﺭﺍﺮﻗﻩﺩﺎﻔﺘﺳﺍﺩﺭﻮﻣﻲﭘﺍﺮﺗﻮﻧﻮﻤﻳﺍﻱﺎﻫﻞﻛﻮﺗﻭﺮﭘﺕﺍﺮﺛﺍ

ﻥﺎﻴﺑﻪﻛﺪﻧﺍﻩﺩﺍﺩﻥﺎﺸﻧﻥﺍﺭﺎﻜﻤﻫﻭﻲﻧﺍﺩﻻ ﻩﺭﺪﻧﺁﻪﻨﻴﻣﺯﻦﻴﻤﻫﺭﺩ .(28

ﺭﺩOX40(CD134)ﻭ CD25ﺪﻨﻧﺎﻤﻫTﻝﻮﻠﺳ ﺖﻴﻟﺎﻌﻓ ﻱﺎﻫﺮﻛﺭﺎﻣ

ﺮﻴﺛﺎﺗ ،ﻥﺎﺴﻧﺍ ﺭﺩ ﻢﻴﺧﺪﺑ ﻱﺎﻣﻮﻧﻼﻣ ﺭﺩ ﻲﺣﺎﺸﺗﺭﺍ ﺪﻴﻳﻮﻔﻨﻟ ﻱﺎﻫﻝﻮﻠﺳ

.(36) ﺩﺭﺍﺩﻥﺍﺭﺎﻤﻴﺑﻱﺎﻘﺑﺮﺑﻱﺮﻴﮔﻢﺸﭼ

ﺶﻘﻧ،(Treg) ﻭCD4

+ CD25+ FOXP3+ﻰﻤﻴﻈﻨﺗTﻯﺎﻫﻝﻮﻠﺳ

Tregﻯﺎﻫﻝﻮﻠﺳ .ﺩﺭﺍﺩ ﻰﻨﻤﻳﺍﻢﺘﺴﻴﺳ ﺯﺎﺘﺳﻮﻣﻮﻫ ﻭ ﻢﻴﻈﻨﺗ ﺭﺩ ﻰﻤﻬﻣ

ﺍﺭ CD4+CD25 T CD8+ﻯﺎﻫﻝﻮﻠﺳﺮﻴﺜﻜﺗﻭﺩﺮﻜﻠﻤﻋ ﺕﺪﺷﻪﺑ

ﻯﺎﻫ ﻝﻮﻠﺳ ﺩﺮﻜﻠﻤﻋﺭﺩ ﺮﻴﮔﺭﺩﻱﺎﻫﻢﺴﻴﻧﺎﻜﻣ .(37) ﺪﻨﻨﻛﻰﻣﺏﻮﻛﺮﺳ

ﻯﺎﻫﻦﻳﺎﻛﻮﺘﻳﺎﺳﺢﺷﺮﺗﺩﻭﺭﻰﻣﻥﺎﻤﮔﻰﻟﻭ ،ﺪﻧﺍﻩﺪﻧﺎﻣ ﻪﺘﺧﺎﻨﺷﺎﻧﻰﻤﻴﻈﻨﺗ

ﻦﻳﺍﺕﺍﺮﺛﺍﺩﺎﺠﻳﺍﺭﺩIL-10ﻭTGF-βﻞﻴﺒﻗﺯﺍﻰﻨﻤﻳﺍﻩﺪﻨﻨﻛﺏﻮﻛﺮﺳ

ﻦﻳﺍﻢﻬﻣﺭﺎﻴﺴﺑﺶﻘﻧﻪﺑﻪﺟﻮﺗﺎﺑﻪﺠﻴﺘﻧﺭﺩ .(38) ﺪﻨﺷﺎﺑﻞﻴﺧﺩﺎﻫﻝﻮﻠﺳﻉﻮﻧ

CD4+FoxP3+ﻱﺎﻫﺖﻴﺳﻮﻔﻨﻟﺪﺻﺭﺩ،ﻲﻨﻤﻳﺍﻢﺘﺴﻴﺳﻢﻴﻈﻨﺗﺭﺩﺎﻫﻝﻮﻠﺳ

ﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻱﺎﻫﻩﻭﺮﮔ .ﺪﺷﻱﺮﻴﮔﻩﺯﺍﺪﻧﺍﻪﻌﻟﺎﻄﻣﺩﺭﻮﻣﻱﺎﻫﻩﻭﺮﮔﺭﺩ

ﻥﺍﺰﻴﻣ ،ﻥﺎﻣﺯﻢﻫﺭﻮﻃﻪﺑﻩﺪﺷﻝﺎﻌﻓCD4++CD8+ﻭ CD4+ﻱﺎﻫTIL

ﻩﻭﺮﮔﺭﺩﺮﻛﺭﺎﻣ ﻦﻳﺍﻥﺍﺰﻴﻣ .ﺪﻧﺩﺍﺩﻥﺎﺸﻧ ﺍﺭﻕﻮﻓ ﺮﻛﺭﺎﻣﺯﺍﻱﺮﺗﻦﻴﻳﺎﭘ

ﻪﻜﻧﺁﻪﺟﻮﺗﺐﻟﺎﺟ .ﺩﻮﺑﺮﺗﻻﺎﺑﻲﻛﺪﻧﺍCD8+ﻱﺎﻫTILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩ

FoxP3ﺯﺍ ﻱﺮﺗﻻﺎﺑﺢﻄﺳ ﺩﺮﻜﻧ ﺖﻓﺎﻳﺭﺩ ﻲﻧﺎﻣﺭﺩ ﭻﻴﻫ ﻪﻛ ﻲﻫﻭﺮﮔ Treg ﻱﺎﻫﻝﻮﻠﺳ ،ﻲﺷﻮﮔﺎﻛﺎﺳ ﻱﺎﻫﻪﺘﻓﺎﻳ ﺱﺎﺳﺍ ﺮﺑ .ﺖﺳﺍ ﻪﺘﺷﺍﺩ

ﺭﻮﻃﻪﺑﻭﺪﻨﻨﻛﻲﻤﻧﺪﻴﻟﻮﺗIL-2،ﻩﺩﻮﺑﻚﻳژﺮﻧﺁﻥﺎﺴﻧﺍﺭﺩCD4+CD25+

ﺐﻟﺎﺟﻉﻮﺿﻮﻣ .(39) ﺪﻨﻨﻛﻲﻣﺭﺎﻬﻣﺍﺭT CD4+ﻱﺎﻫﻝﻮﻠﺳﺮﻴﺜﻜﺗﻲﺗﺍﺫ

ﺕﺭﻮﺻ ﻪﺑ ﻪﻛTreg CD4+CD25+ﻱﺎﻫﻝﻮﻠﺳ ﻪﻛﺖﺳﺍﻦﻳﺍﻪﺟﻮﺗ

ﺭﺩ ﻲﺘﺣ ﺍﺭ ﺩﻮﺧﻱﺮﮔﺏﻮﻛﺮﺳﻲﻳﺎﻧﺍﻮﺗ ،ﺪﻧﺍﻪﺘﻓﺎﻳ ﺵﺮﺘﺴﮔ ﻲﻨﺗﻥﻭﺮﺑ

ﻪﻛﻩﺪﻫﺎﺸﻣﻦﻳﺍ .ﺪﻨﻨﻛﻲﻣﻆﻔﺣﻩﺪﺷﻝﺎﻌﻓﻩﺮﻃﺎﺧTﻱﺎﻫﻝﻮﻠﺳﻞﺑﺎﻘﻣ

ﻱﺎﻫﺦﺳﺎﭘﻭﺪﻨﺑﺎﻳﺵﺮﺘﺴﮔﻥﺪﺑﺯﺍﺝﺭﺎﺧﺭﺩﺪﻨﻧﺍﻮﺗﻲﻣTregﻱﺎﻫﻝﻮﻠﺳ

ﻱﺍﺮﺑﻱﺩﺎﻳﺯ ﻲﻨﻴﻟﺎﺑ ﻱﺎﻫﺩﺮﺑﺭﺎﻛ،ﺪﻨﻨﻛ ﻢﻴﻈﻨﺗ ﺍﺭﻩﺮﻃﺎﺧ T ﻱﺎﻫﻝﻮﻠﺳ

ﻱﺎﻫﻝﻮﻠﺳﺎﻬﻧﺁﺭﺩﻪﻛﻲﻳﺎﻫﻱﺭﺎﻤﻴﺑﻥﺎﻣﺭﺩﻱﺍﺮﺑﺎﻫﻝﻮﻠﺳﻦﻳﺍﺯﺍﻩﺩﺎﻔﺘﺳﺍ

ﻪﻴﻠﻋ ﺲﻧﺍﺮﻟﻮﺗﻱﺎﻘﻟﺍ ﻦﻴﻨﭽﻤﻫ ،ﺪﻨﻛﻲﻣ ﺩﺎﺠﻳﺍ ﻩﺩﻮﺑﻱﺭﺎﻤﻴﺑ ﺐﺒﺴﻣ T

ﻩﺪﻨﻳﺁﺭﺩﺎﻫﻝﻮﻠﺳﻉﻮﻧﻦﻳﺍﺩﺮﺑﺭﺎﻛﻩﺪﻤﻋﺩﺭﺍﻮﻣﺯﺍﺰﻴﻧﻱﺪﻧﻮﻴﭘﻱﺎﻫﺖﻓﺎﺑ ﻪﻛﺪﻧﻮﻴﭘﻥﺎﮔﺪﻧﺮﻴﮔﺭﺩFoxP3ﺢﻄﺳﻪﻛﻩﺪﺷﻩﺩﺍﺩﻥﺎﺸﻧ .ﺩﻮﺑﺪﻫﺍﻮﺧ

ﺶﻴﺑﺮﺑﺍﺮﺑ 100 ﺐﻳﺮﻘﺗﺭﻮﻃﻪﺑ،ﺪﻨﺘﺷﺍﺩﻞﻤﺤﺗﻩﺪﺷﺪﻧﻮﻴﭘﺖﻓﺎﺑ ﻱﺍﺮﺑ

ﻦﻜﻤﻣ،ﺩﻮﺟﻭﻦﻳﺍﺎﺑ .(40) ﺪﻧﺍﻩﺩﺮﻛﺩﺭ ﺍﺭﺪﻧﻮﻴﭘ ﻪﻛﺖﺳﺍﻱﺩﺍﺮﻓﺍﺯﺍ

ﻪﻴﻠﻋﻲﻨﻤﻳﺍﻢﺘﺴﻴﺳﻲﻠﺻﺍﺶﻨﻛﺍﻭﻡﺪﻋﻲﻠﺻﺍﻊﻧﺍﻮﻣﺯﺍﺎﻫﻝﻮﻠﺳﻦﻳﺍﺖﺳﺍ ﺪﻧﺍﻩﺩﺍﺩﻥﺎﺸﻧ ﻥﺍﺭﺎﻜﻤﻫﻭﻮﻳﮓﻨﻴﭘﻪﻜﻧﺎﻨﭼ؛ﺪﻨﺷﺎﺑﻱﺭﻮﻣﻮﺗﻱﺎﻫﻝﻮﻠﺳ ﻲﻤﻴﻈﻨﺗﻱﺎﻫﻝﻮﻠﺳ ﺎﺗﺪﻤﻋﻪﻛ) CD4+ﻱﺎﻫﻝﻮﻠﺳ ﺯﺍﺭﻮﻣﻮﺗﻪﻴﻠﺨﺗﻪﻛ

ﻭ ﻲﻳﺎﻬﻧﻞﺣﺍﺮﻣﺭﺩﻲﺘﺣﺪﻧﻮﻴﭘﻊﻓﺩ ﺚﻋﺎﺑ،ﺭﻮﺘﻜﻓﺍﻪﻠﺣﺮﻣﺭﺩ (ﺪﻨﺘﺴﻫ

ﺪﻧﺍﻩﺩﺍﺩﻥﺎﺸﻧ ﻥﺍﺭﺎﻜﻤﻫﻭ ﻮﺗﺎﺳﻲﭽﻳﺍ .(41) ﺩﺩﺮﮔﻲﻣﺭﻮﻣﻮﺗﻪﺘﻓﺮﺸﻴﭘ

ﻲﻬﮔﺁﺶﻴﭘﺎﺑ،ﻲﻤﻴﻈﻨﺗﻱﺎﻫﻝﻮﻠﺳﻪﺑ CD8+ﻱﺎﻫﻝﻮﻠﺳﻱﻻﺎﺑﺖﺒﺴﻧﻪﻛ

ﺭﺎﻤﻴﺑﺮﻤﻋﻝﻮﻃﺶﻳﺍﺰﻓﺍﺚﻋﺎﺑﻭﻩﺩﻮﺑﻩﺍﺮﻤﻫﻥﺍﺪﻤﺨﺗﻥﺎﻃﺮﺳﺭﺩﻱﺮﺘﻬﺑ

.(42) ﺩﺩﺮﮔﻲﻣﺰﻴﻧ

ﺖﻓﺎﻳﺭﺩ ﻩﻭﺮﮔ ﺭﺩ ﺕﺎﻧﺍﻮﻴﺣ ﺮﻤﻋ ﻝﻮﻃ ﻭ ﺭﻮﻣﻮﺗ ﺪﺷﺭ ﺖﻋﺮﺳ

TIL ﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩ ﻩﻭﺮﮔﻪﺑﺎﺸﻣﻩﺪﺷﻝﺎﻌﻓCD4+ﻱﺎﻫTIL ﻩﺪﻨﻨﻛ

CD4++CD8+ ﻩﻭﺮﮔ ،ﺪﻌﺑ ﻪﺟﺭﺩ ﻭ ﻩﺩﻮﺑ ﻩﺪﺷ ﻝﺎﻌﻓ CD8+ ﻱﺎﻫ

TIL ﻩﺪﻨﻨﻛ ﺖﻓﺎﻳﺭﺩﻩﻭﺮﮔ ﺮﻤﻋﻝﻮﻃ،ﺭﺎﻈﺘﻧﺍﻑﻼﺧﺮﺑ .ﺖﺷﺍﺩﺭﺍﺮﻗ

ﺩﺍﺪﻌﺗ ﻪﻜﻨﻳﺍ ﻪﺑ ﻪﺟﻮﺗ ﺎﺑ .ﺩﻮﺑ ﺮﺘﻤﻛ ﻩﺪﺷ ﻝﺎﻌﻓCD4++CD8+ﻱﺎﻫ

،ﻩﺩﻮﺑﺮﮕﻳﺩﻱﺎﻫﻩﻭﺮﮔﺮﺑﺍﺮﺑﻭﺩﻩﻭﺮﮔﻦﻳﺍﻪﺑ ﻩﺪﺷﻖﻳﺭﺰﺗﻱﺎﻫﻝﻮﻠﺳ

ﻪﻛﻩﺪﻳﺩﺮﮔ ﺲﻳﺯﺎﺘﺳﻮﻣﻮﻫﻱﺎﻫﻢﺴﻴﻧﺎﻜﻣﻥﺪﺷﻝﺎﻌﻓﺐﺒﺳ ﺮﻣﺍ ﻦﻴﻤﻫ

ﻝﺎﻤﺘﺣﺍ ﻪﺑ .ﺖﺳﺍﻩﺪﺷﻥﺎﻣﺭﺩﻪﺠﻴﺘﻧﺶﻫﺎﻛﻭﺎﻫﻝﻮﻠﺳﺯﻮﺘﭘﺎﭘﺁﺚﻋﺎﺑ

ﻦﻳﺍ ﻲﻟﺎﺤﻃﻱﺎﻫﻝﻮﻠﺳﺭﺩCD25+ﻱﺎﻫﻝﻮﻠﺳﺩﺍﺪﻌﺗﻥﺩﻮﺑ ﻢﻛﺩﺎﻳﺯ

ﻱﺮﺘﺸﻴﺑ ﻱﺎﻫﻲﺳﺭﺮﺑ ﺪﻨﻣﺯﺎﻴﻧ ﻪﺘﺒﻟﺍ ﻪﻛ ﺪﺷﺎﺑﻲﻣ ﺎﺘﺳﺍﺭ ﻦﻳﺍ ﺭﺩ ﻩﻭﺮﮔ

.ﺪﺷﺎﺑﻲﻣ

ﻯﺮﻴﮔ

ﻪﺠﻴﺘﻧ

ﻥﺍﻮﺗﻲﻣ ﻪﻛ ﺖﻓﺮﮔ ﻪﺠﻴﺘﻧ ﻥﺍﻮﺗﻲﻣ ﺮﺿﺎﺣ ﻪﻌﻟﺎﻄﻣ ﺯﺍ ﻉﻮﻤﺠﻣﺭﺩ

ﺭﺩ ﻲﻨﻤﻳﺍﻢﺘﺴﻴﺳﻩﻮﻘﻟﺎﺑ ﻩﺪﻨﻨﻛﻝﺎﻌﻓﻚﻳﻥﺍﻮﻨﻋﻪﺑ ﺍﺭﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣ

ﻞﻣﺍﻮﻋ .ﺖﻓﺮﮔﺭﺎﻛﻪﺑﺎﻫﻥﺎﻣﺭﺩﻉﻮﻧ ﻦﻳﺍﺭﺩﻭﺩﺮﻛﻲﻘﻠﺗﻲﭘﺍﺮﺗﻮﻧﻮﻤﻳﺍ

ﺪﻧﺮﻴﮔﻲﻣﺭﺍﺮﻗﻩﺩﺎﻔﺘﺳﺍ ﺩﺭﻮﻣﻲﻨﻤﻳﺍﻢﺘﺴﻴﺳﻥﺩﺮﻛﻝﺎﻌﻓﻱﺍﺮﺑﻲﻔﻠﺘﺨﻣ ﻥﺎﻣﺭﺩﻪﺠﻴﺘﻧﺮﺑﺪﻧﺍﻮﺗﻲﻣ،ﺎﻫﻪﻨﻳﺰﮔﺮﻳﺎﺳﻦﻴﺑﺯﺍﻪﻨﻳﺰﮔﻚﻳﺏﺎﺨﺘﻧﺍﻪﻛ ﻥژﻭﺪﻧﺁﺪﻴﻳﻮﻴﭘﺍﻚﻳﺯﺍﺭﺎﺑﻦﻴﻟﻭﺍﻱﺍﺮﺑﺮﺿﺎﺣﻪﻌﻟﺎﻄﻣﺭﺩ .ﺩﺭﺍﺬﮕﺑﺮﻴﺛﺎﺗ

ﺭﺩ .ﺪﺷ ﻩﺩﺎﻔﺘﺳﺍ ﺎﻫﺖﻴﺳﻮﻔﻨﻟ ﻥﺩﺮﻛ ﻝﺎﻌﻓ ﻱﺍﺮﺑ ﻲﻨﺗﻥﻭﺮﺑ ﺕﺭﻮﺻ ﻪﺑ

ﺚﻋﺎﺑ ﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﻦﻴﻳﺎﭘ ﻱﺎﻫﺯﻭﺩﻩﺪﻣﺁ ﺖﺳﺩﻪﺑ ﺞﻳﺎﺘﻧ ﻱﺎﺘﺳﺍﺭ

ﻥﺎﺸﻧ ﻲﻠﺒﻗ ﺕﺎﻌﻟﺎﻄﻣ ﻑﻼﺧﺮﺑ ﻲﻟﻭ ،ﺩﻮﺷﻲﻣ ﺎﻫﺖﻴﺳﻮﻔﻨﻟ ﻥﺪﺷ ﻝﺎﻌﻓ

ﻲﻨﻤﻳﺍﻢﺘﺴﻴﺳﺭﺎﻬﻣﺚﻋﺎﺑ،ﺭﺎﻤﻴﺗﻩﺎﺗﻮﻛﻱﺎﻫﻥﺎﻣﺯﺕﺪﻣﻪﻛﺪﻧﺩﻮﺑﻩﺩﺍﺩ ﻦﻳﺍﺭﺩ .ﺩﻮﺷﻲﻣﻲﻨﻤﻳﺍﻢﺘﺴﻴﺳﺖﻳﻮﻘﺗﺚﻋﺎﺑﺭﺎﻤﻴﺗﻲﻧﻻﻮﻃﻱﺎﻫﻥﺎﻣﺯﻭ

ﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﺎﺑﺭﺎﻤﻴﺗﻲﻧﻻﻮﻃ ﻱﺎﻫﻥﺎﻣﺯﻪﻛﺪﺷﻩﺩﺍﺩﻥﺎﺸﻧ ﻪﻌﻟﺎﻄﻣ

ﻝﺎﻌﻓﻢﻬﻣﻱﺎﻫﺭﻮﺘﻛﺎﻓﺯﺍﻲﻜﻳﻥﺍﻮﻨﻋﻪﺑCD25ﺶﻳﺍﺰﻓﺍﺚﻋﺎﺑﺎﻬﻨﺗﻪﻧ

(9)

ﺭﻮﺘﻛﺎﻓ ﻱﺎﻘﻟﺍ ﻚﻳﺮﺤﺗ ﺭﺩ ﻩﺎﺗﻮﻛ ﻱﺎﻫﻥﺎﻣﺯ .ﺩﺩﺮﮔﻲﻣ ﺭﺎﻤﻴﺗ ﺯﺍ ﻞﺒﻗ

TILﻩﺪﻨﻨﻛﺖﻓﺎﻳﺭﺩﻱﺎﻫﻩﻭﺮﮔﺭﺩﻪﻛﻲﺗﻭﺎﻔﺘﻣﺞﻳﺎﺘﻧﻲﻃﺮﺗﺮﺛﻮﻣﻕﻮﻓ

ﺖﺳﺩﻪﺑﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﺎﺑﻩﺪﺷﻝﺎﻌﻓCD8+ﻱﺎﻫTILCD4+ﻱﺎﻫ

ﻱﺎﻫﻪﻋﻮﻤﺠﻣﺮﻳﺯﻱﻭﺭﻦﻴﻟﺎﻔﻜﻧﺍ - ﺖﻣﺮﺛﺍﻥﺍﺰﻴﻣﻭﻩﻮﺤﻧﺭﺩﺪﻳﺎﺑ،ﻩﺪﻣﺁ

.ﺩﻮﺷﻮﺠﺘﺴﺟﻲﺘﻴﺳﻮﻔﻨﻟ

ﺮﻜﺸﺗ

ﺮﻳﺪﻘﺗ

3340 ﻱﺎﻫﻩﺭﺎﻤﺷﻪﺑﻥﺍﺮﻬﺗﻲﻜﺷﺰﭘﻡﻮﻠﻋﻩﺎﮕﺸﻧﺍﺩﺖﻧﺍﺮﮔﺎﺑﺡﺮﻃﻦﻳﺍ

ﺯﺍﺍﺭﺩﻮﺧﺮﻜﺸﺗﻭﺮﻳﺪﻘﺗﺐﺗﺍﺮﻣﻥﺎﮔﺪﻨﺴﻳﻮﻧ .ﺖﺳﺍﻩﺪﺷﻡﺎﺠﻧﺍ 5988 ﻭ

ﻩﺮﻫﺎﻃﻢﻧﺎﺧﻭﻱﻭﺪﻬﻣﻱﺪﻬﻣ،ﻦﺴﺣﺮﻴﻫﺯﺮﺘﻛﺩﻥﺎﻳﺎﻗﺁﻱﺎﻫﺕﺪﻋﺎﺴﻣ

.ﺪﻧﺭﺍﺩﻲﻣﻥﺎﻴﺑﻲﻠﺿﺎﻓﻮﺑﺍ

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