APC targeted Ag: can it direct Th1 or Th2 responses

[Mohan]

The answer to the question, Can B7-1 and B7-2 costimulate Th cells
differentially into Th-1 or Th-2?, is propably No. The mechanism of
Th-1 and Th-2 differentiation is much more complex and not yet
completely understood  than the simple notion that B7-1 or B7-2
costimulation will lead to differential Th phenotypes.

Studies using antibodies to differentially block B7-1 or B7-2 (and
looking for what type of Th lineage results) in disease models have
shown contradicting results (Kuchroo et.al. Cell 80:705, 1995 vs
Lenschow et.al. J.Exp.Med. 181:1145, 1995). 

Kuchroo et.al. have proposed B7-1 costimulation leads to Th-1 and B7-2
leads to Th-2. A variant of this hypothesis, B7-2 directs immune
response to Th-2 and B7-1 is a more neutral signal is proposed by
Freeman et. al. (Immunity 2:523, 1995). Both these views are not
propably correct if you look at the following results from other
studies.

Levine et.al. (Int.Immunol. 7:891, 1995) using similar experimental
system of that of Freeman et.al. have found no qualitative difference
between human  B7-1 and B7-2 in their ability to costimulate different
T cell populations. Also, results obtained in our lab (unpublished)
shows that both murine B7-1 and B7-2 have the potential to induce IL-4,
a Th-2 marker cytokine in CD4 T cells.

For a good review on this topic read Cell, 80:979, 1995.

Mohan     

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Mohan Natesan Ph.D.
D1002 DFCI
44 Binney St
Boston MA 02115
mohan_natesan at dfci.harvard.edu