   1 
 


  2019     Nature    ,    1  ,    ,         .     . . 4-          ,                 8 .





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 ,2019

 ,  ,2019



ISBN978-5-4496-4499-2

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1.  1-      , .



2.  ,  , .



3.      ,      :

https://www.ncbi.nlm.nih.gov/pubmed/26863486?fbclid=IwAR0_xLRtaCwzngIbU5Kz_ch_oQkq_iF708qKzOisfVjAK-k1vxj0ksQIIMc (https://www.ncbi.nlm.nih.gov/pubmed/26863486?fbclid=IwAR0_xLRtaCwzngIbU5Kz_ch_oQkq_iF708qKzOisfVjAK-k1vxj0ksQIIMc)



4.       :

 (,      ,   );

 (,     ):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860878/?fbclid=IwAR2zvRlddgN0wXH07gcacDUPclLiGVkpSe17_z7BWOIdVZXnNfTLBUux6b4 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860878/?fbclid=IwAR2zvRlddgN0wXH07gcacDUPclLiGVkpSe17_z7BWOIdVZXnNfTLBUux6b4)

5.        :

  ( );

     ();

     /.



  2018      ꠖ ---,   .    ---  TIGIT,     ,   :

https://www.frontiersin.org/articles/10.3389/fimmu.2018.02783/full?fbclid=IwAR2P7oc36Ic1s3Wvjg_UahUhdiD4kI-Q1jxEfadRWOxmnE1f5dqP3hzHECk (https://www.frontiersin.org/articles/10.3389/fimmu.2018.02783/full?fbclid=IwAR2P7oc36Ic1s3Wvjg_UahUhdiD4kI-Q1jxEfadRWOxmnE1f5dqP3hzHECk)

  ,        .       (  ) ,        .




  


  ,        ?  -     (     ).         ,     .      堖  ,     .             ,     -     1-    .     .

   -    CD4 -   MHC-II-       ,    . MHC-       ?-  ,   ,    ,     .    ,    ?-ꠖ   N-CAM. -     ?-,      .

      .       50%  -,        .

,    CTLA4,     -,     .       .

  L1,            .

  GCK,  ,  MODY.

     1-    ,  .         ( B1)   ?-,    ࠖ  ()  -?,       .     :           .

     1-    .    1-           .      Bacteroidetes/Firmicutes  ,   . Ӡ       .    ,        (, ). .   .

      .     , ,    ,      1- . -     .




 


     1- .        ()     .       .    .     :    CD3 (-CD3 )     1(IL-1RA).

    -, - ?-,     -   ,   .         ,       CpG-   GpG-,   -  .

     1- ࠖ       -.  -      CD3 (. cell differentiation  ).   ,    -         .   CD3.

    ,   :

;

;

   / .



        .              -,     . ,  (),  ()         1- . ,     ,       1- , ,       .     1-      ,     .     :    CD3 (-CD3 )     1(IL-1RA):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774222/?fbclid=IwAR0wF4hSYT5tjRd5qK-YNZceophX83UdhjnJsvWR8wml8eMZOFMGcqlL53w (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774222/?fbclid=IwAR0wF4hSYT5tjRd5qK-YNZceophX83UdhjnJsvWR8wml8eMZOFMGcqlL53w)




   1-  


 ,         -  (),     .

         ,      ,   .       ,   , - ,  (2005)        1-    .     .        . ,        IL1, 6, 18.    :

  10/


  ;     ; 堖    ;

  3/,    (   ):  0, 26  6.



:



         ?- ,   1- ,     -;      ;   -      ( 0,1/)   :

http://www.dissercat.com/content/

immunosupressivnaya-terapiya-v-kompleksnom-

lechenii-sakharnogo-diabeta-1-go-tipa-u-detei-0?

fbclid=IwAR0_vBXUASfNXT9Yoe_

N0w6VOFK1z8llz6d2HoafBfjbW8iEkQsBEZdKY70#



  ,       Foxp3+Treg      :

https://www.ncbi.nlm.nih.gov/pubmed/23403703?fbclid=IwAR2yYZ4N2B_gZtBBHrJvaR046KUJT7bDVlikPyJIWRGpsXccZrIgkT0L4e4 (https://www.ncbi.nlm.nih.gov/pubmed/23403703?fbclid=IwAR2yYZ4N2B_gZtBBHrJvaR046KUJT7bDVlikPyJIWRGpsXccZrIgkT0L4e4)



   -            :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836708/?fbclid=IwAR1okJk9fin9hng1N5Uy2Xsj6sHm-me-sQ1f_1a2RRQoU8eOHm-KUAiNrgs (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836708/?fbclid=IwAR1okJk9fin9hng1N5Uy2Xsj6sHm-me-sQ1f_1a2RRQoU8eOHm-KUAiNrgs)




  


     ,    .         120頖           .   1-          :

堖    ,      . ,  ,   ,   ,    ?-,      .

堖  .      ?-,    ?- , ,    .     ,           .      A(CsA)    .   CsA    ,    ,    .      ,   .

         ?-.  ,    1D  ,   -.      ?-    ,   :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105696/?fbclid=IwAR0_lxGwQm_Bj7?SnT4dG0vPLNhxS-HhzTGmv-1RqpxixEGESeIdUFwb8mk




 .     HLA-DQ8-


    II  ( II)    .  ,    1-   DQ8    60% .   (David A. Ostrov, Aaron W. Michels et al.)  10   ,   DQ8, invitro invivo.    ࠖ    50   .   ,     DQ8   ,     T- ?-,               .    invitro    1b-.    20DQ8-    1-   18 46         .    12,    . Ӡ1720     DQ8   40%,      :

https://www.jci.org/articles/view/97739 (https://www.jci.org/articles/view/97739)








 

?-


    -CD3-mAb  TCDAb+TNF-?-i :

https://onlinelibrary.wiley.com/doi/full/10.1111/j.1600-6143.2011.03977.x (https://onlinelibrary.wiley.com/doi/full/10.1111/j.1600-6143.2011.03977.x)



   -            :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836708 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836708)



   1-   IL6:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5253293 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5253293)



 GAD65.  ,   GAD65- -    .    GAD65-    , .       D   ,    ,   ?-   ,    D.          2022,      .    GAD65--   -  0,12/  (0,36 ).    4 GAD65            .      D ()   (2000 )   ,     .     -       .  15   -       34%  - .        :

https://www.nejm.org/doi/full/10.1056/NEJMc

1616343?bclid=IwAR3hmCzozU5KmCcqcGx6uPCOS7

Cul5K4MgxxqzAFQQ5w7HKhJ5aFaYajwAs

 -       1- :

https://www.ncbi.nlm.nih.gov/pubmed/21864264?

fbclid=IwAR3tdgnmiI07Ld35ld8DfRnttdaEIbQv5Igl

C53QeMDztVDFGJfvC6tJls0



   -    1- :

https://www.ncbi.nlm.nih.gov/pubmed/16318986?

fbclid=IwAR1bpxc7NKbRWxU3J2NEEPMKJ1LQtfNOJ

jEgB6kxLCAAODFzbeWNQADec3A



  ,      1- ,      -FcR- -CD3-  (mAb):

https://www.ncbi.nlm.nih.gov/pubmed/19203097?fbclid=IwAR3ESqZf33QPEySjmYvQYvBbotmp0wHIOk9_swvpuwFCsdFJLJ0VsuGEIhI (https://www.ncbi.nlm.nih.gov/pubmed/19203097?fbclid=IwAR3ESqZf33QPEySjmYvQYvBbotmp0wHIOk9_swvpuwFCsdFJLJ0VsuGEIhI)



    1-   ࠖ    .  ,  ?-,   -.    ?-    .

   27  ( 100)   1- .           .       .

 12          50%,  ,  ,  .     ?-  .      :

http://stm.sciencemag.org/content/9/402/

eaaf7779.full? fbclid=IwAR3UvlPLgVavUId61

5QcPm7rxuQAzT4t7UqSB_6K7ZHXnDdk0N6r7zuTmw



  T1D.       Foxp3+Treg       :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700020/?fbclid=IwAR3Q5hzxt63SG6v5L6L-U6_olsoYI_y2bXdJwLh4CbPnqXEkMlcdSa0LQQ4 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700020/?fbclid=IwAR3Q5hzxt63SG6v5L6L-U6_olsoYI_y2bXdJwLh4CbPnqXEkMlcdSa0LQQ4)



 , -,   -    ?-:

http://stm.sciencemag.org/content/9/402/

eaaf7779.fullfbclid=IwAR1LOm7OUHbIyd-1NsKP2

Tnxpy9o1ZmZG5AS8TJn91T7hBR97tOizgPp1s4



   -            :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836708/?fbclid=IwAR2_Xr_78r1B02qzPhXFwV-udxLM-iYJZIHhsSl0G91DYPiOJIjcu72uLCo (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836708/?fbclid=IwAR2_Xr_78r1B02qzPhXFwV-udxLM-iYJZIHhsSl0G91DYPiOJIjcu72uLCo)



  :

http://stm.sciencemag.org/content/9/402/eaaf7779.full (http://stm.sciencemag.org/content/9/402/eaaf7779.full)



 / (bortezomib)  1- :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736230/?fbclid=IwAR3WhOQ3HdJecvn4ueFokDiE_tHeNxvls775Wu8lAICJWZ3vAousgfCtecM (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3736230/?fbclid=IwAR3WhOQ3HdJecvn4ueFokDiE_tHeNxvls775Wu8lAICJWZ3vAousgfCtecM)



   1- :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5253293 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5253293)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125295 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125295)



   1- :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860

878/?fbclid=IwAR3P05T1K0M-yor8TvgluRxCf_

fsnIu-BZ5tHcgl_fYIHCMh5x0tdcAFKOc



     1- :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752911/?fbclid=IwAR04LerTJ2wpRBDsNC_ShQY9ZmmyS3xgBgN1ZARdcsaQI8YGpfjEIiMCF78 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752911/?fbclid=IwAR04LerTJ2wpRBDsNC_ShQY9ZmmyS3xgBgN1ZARdcsaQI8YGpfjEIiMCF78)



    1- :

https://www.ncbi.nlm.nih.gov/pmc/articles/

PMC5774222/fbclid=IwAR1Sf8Rs1FlU7pXUqZzn2shSj

TeNR3eIxz6xalvL1QpOnUS3WrbhwTevxDI



   1-  :          IL8, IL-1Ra, MCP-1MIP-1?   1- :

https://www.ncbi.nlm.nih.gov/pubmed/26158606?

fbclid=IwAR3V632CAdfoXj1138A1OHz6NdhI

XovmphkIne4gn7Q17svtOoXgH2aPgx0



 :           -CD3- ,  -    1- .          ,    .       mAb  CD20,  -. ,      ?- mAb,   -2,    , ,       mAb,  T-  B-.  , mAb       (        )   1-  , ,   ,  ,      :

https://www.ncbi.nlm.nih.gov/pubmed/19642469?

fbclid=IwAR2WD6fqD2-3-12MVsET_LYvq4m3Lg2mublz

EwtMQ4v887StxDpIFxxy_Mo



   CD3 (mAb)        -.  ,  -CD3-mAb    ,   .           1-    .          .    -FcR- -CD3-mAb ,  mAb    -,     -10(IL-10)  -? (IFN-?) invitro  FcR- -CD3-mAb   IL-10, IL-5,  IFN-?  IL-2  .  ,     CD4+IL-10+CCR4 invivo.    ,  -CD3-mAb    -,         1- .        -CD3-mAb   :

https://www.ncbi.nlm.nih.gov/pubmed/14610290?fbclid=IwAR0IiMcuUN5TUfjU_Isq2ExOBoWgb6ckPE6gi-8ElCxlyEW5px7RqI_apHs (https://www.ncbi.nlm.nih.gov/pubmed/14610290?fbclid=IwAR0IiMcuUN5TUfjU_Isq2ExOBoWgb6ckPE6gi-8ElCxlyEW5px7RqI_apHs)



  1-  :  ,     ?-     .

   1- :   ,       Foxp3+Treg      :

https://www.ncbi.nlm.nih.gov/pubmed/23403703?

fbclid=IwAR2QMC4yuJO5nHDIaq56OLwhQAU31Fhu

7G0oLiaBFzuyqlFhKMbXTqRzncY



    ?-:     -CD3-mAb  TCDAb+TNF-?-i :

https://onlinelibrary.wiley.com/doi/full/10.1111/j.1600-6143.2011.03977.x (https://onlinelibrary.wiley.com/doi/full/10.1111/j.1600-6143.2011.03977.x)



   1- :      1-        .   ,  - ,   ,    .                DR4 (HLA-DR4),   (C19-A3).           ,              invitro.    1-   HLA-DRB1*0401 30 (n=18)  300 (n=18)     0, 12    (n=12).             / ,  -.  -,  -  -10(IL-10),    418    (  12 , P = ).   IL-10      03 (P=0,05  5-- invitro),     36 (P=001  10-- invitro).          ,    ,  -     -   ?- :

https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2249.2008.03814.x (https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2249.2008.03814.x)




   


               .

  ,    ,  .       ,     . Ѡ    ...ĸ..       1-  .     1-          (-  0,1/)        ,      1- .

 ,       ,       ,   ,     ,   , , .  ,  .      ,    ,    蠖   ,           . ,  - ,    ,      . ,    ,    .

     ,  ,      .  , Diamyd,   : Orphan Drug Designation  FDA.   III  DIA-AID: DiaPep277 Arresting Immune Diabetes (      DiaPep277)  .



:

..     1- . , 2013, 2(22).



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        1- .         ,     ,   .








 1948    ,  ,    Victory.    ,     25,      ,    ,  50,  75.     40,  50- ,    65,  75.   ,     ,      .  ,         :

https://link.springer.com/article/10.1007%2Fs00125?

018-4664-5?fbclid=IwAR26E0OHN-VZmMJKzG-

CMcBk5ysF3b_7RZc8o_vxlfs3_Zwqr5c9bIz3jRw



  蠖     , ,      ,  .   20172019          1- 2- .



-,         2- .

-,       ,    () , ,    1-    . 堖          ()     (),     .

-,       ,     ,    ,   1999  :    1- ࠖ   ,   ,  !

       2019      Nature:

https://www.nature.com/articles/s41556-018-0216-y (https://www.nature.com/articles/s41556-018-0216-y)



Ƞ  .        .    ,     :    ?-   ?- ,  ,       (),     ().

  ,    GABA   ?- ?- .  : http://www.cell.com/cell/fulltext/S0092-8674(16)31523-9 (http://www.cell.com/cell/fulltext/S0092-8674(16)31523-9) ,    ?-    ?-          GABA ,    ?-   ?-,      ?- ?-  .  ,     GABA       ?- ,   1- 2- .

       ( , CRISPR/Cas),    () , , ,   ,     ,    - :

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(17)30492-8 (https://www.cell.com/cell-metabolism/fulltext/S1550-4131(17)30492-8)



       :        ?-  .    5% 18% ?-     (DYRK1A) TGFbSF:

https://www.sciencedirect.com/science/article/pii/S1550413118307423?dgcid=rss_sd_all (https://www.sciencedirect.com/science/article/pii/S1550413118307423?dgcid=rss_sd_all)



     ,      ,       :    130%:

https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(18)30379-9 (https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(18)30379-9)



   ?-    1- 2- :   ?-    insitu        .  ,     2(ICR2)     ?-. ,            .          ?-  :

https://jci.org/articles/view/124583fbclid=IwAR2

Bk5zupUDnlusD3iRS-1DQKn1DiJ3AAlPqFccI2qeEx

He6o3cPgrmJ6Yk



 :         ,   ,     ,      .         ,     :  , ,  堖 , , .

Ѡ ,   ,   , ,     ,  ,            -,     .  ,     ,  ,           , ,    :   .   ,     ,  .

,       ,      .            :   ,     . Ƞ      ,    ,    .  ,  ,      .       ,    ,   :    젖  ,   .




  .


   .

   ,     (https://www.litres.ru/uriy-zaharov-1250948/immunoterapiya-saharnogo-diabeta-1-tipa-seriya-dokaza/)  .

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