T cell co-stimulation/anergy

[Lee Wetzler]

Dr. Colin R.A. Hewitt (crah1 at leicester.ac.uk) wrote:
: Date:          25 Jan 1994 03:14:53 -0000
: From:          dexper at wrair-emh1.army.mil
: Reply-to:      dexper at wrair-emh1.army.mil
: To:            "bionet.immunology mail newsgroup" <bionet-news at daresbury.ac.uk>
: Subject:       Re: Something unknowable in immunology? Simple logic?

: dexper at wrair-emh1.army.mil writes:

: >According to Liu and Janeway (PNAS 89:3845 1992), the antigens
: >and the costimulatory molecules must be on the same cell for clonal expansion
: >of T cells, which explains why tissues can express autoantigens and contain
: >active antigen-presenting cells without inducing autoimmunity. 

: Harding et al (Nature, p607, 356, 1992) used plastic coated anti CD3 as an "antigen"
: and LPS blasts as providers of costimulation to induce T cell activation. These 
: signals are effectively on "different cells", how does this square with the need for the 
: two signals on the same cell??


: Dr. Colin R.A. Hewitt
: University of Leicester/MRC
: Centre for Mechanisms of Human Toxicity
: Hodgkin Building
: PO Box 138
: Lancaster Rd
: LEICESTER
: LE1 9HN
: U.K.

: Phone +44 (0)533 525587
: Fax +44 (0)533 525616
: E-Mail crah1 at le.ac.uk.

Colin, CD3 crosslinking is used as a mimic of "Signal 1" by cross linking the 
T cell receptor.  This is strictly an in vitro model and almost assuredly does
not happen in vivo.  Signal 1 gives specificity to the expansion of T cells,
and cross-linking with with anti-CD3 mAb is certainly non-specific.  
Costimulatory activity can also be mimicked by using transfectants that are 
deficient in B7 or B7-2 and supply signal 2 with anti-CD28 mAb.  I hope this 
helps a little, but if not please ask more.

Lee Wetzler
The Maxwell Finland Laboratory for Infectious Diseases
Boston City Hospital
Boston University School of Medicine
email lwetzler at acs.bu.edu
phone 617-534-4394