Immunology help :P

[SB100]

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I have no idea where to post this, but my mentor at the NIH posed an interesting question to me. I was reading some literature before about IL-2 and how it signals for T cell differentiation in immune response. There was an experiment performed (found in the book "Cytokine Knockouts") where they knocked out each gene used to express part of the IL-2 receptor (IL-2R) in mice and expected that due to the inability to bind IL-2, T cell differentiation would not occur and the mice would die because they would have no immune response. Instead, they found the mice died from inflammation of several organs as a result of significant increases in T cell count. However, when performed in vitro, this did not occur. Any ideas why?

 

[bottles999]

I have no idea where to post this, but my mentor at the NIH posed an interesting question to me. I was reading some literature before about IL-2 and how it signals for T cell differentiation in immune response. There was an experiment performed (found in the book "Cytokine Knockouts") where they knocked out each gene used to express part of the IL-2 receptor (IL-2R) in mice and expected that due to the inability to bind IL-2, T cell differentiation would not occur and the mice would die because they would have no immune response. Instead, they found the mice died from inflammation of several organs as a result of significant increases in T cell count. However, when performed in vitro, this did not occur. Any ideas why?

That study is correct. It turns out IL-2 has a redundant backup that is used for many, but not all, of its functions - IL-15. In summary, IL-2 and IL-15 both can regulate:
1. Proliferation/Activation of B & T cells
2. Ig Systenthesis in B-Cells
3. Induce CTLs

IL-2 ONLY functionality
1. implicated in Activated-Induced Cell Death (AICD) - Related to over active TCR response and a limit to autoreactivity
2. Required for Tregs maintance that are CD-25+ (High) which is the IL-2receptor and NEVER make their own IL-2 due to repression from foxp3.

So by knocking out IL-2 cytokine, one apparently loses a class of T-cells called tregs. This condition results in rampant/multi organ autoimmune attack against self, since Tregs suppress the activation of autoreactive Tcells. This condition is similar to IPEX (Immune dysregulation, polyendcroneopathy X-linked) syndrom, which is caused by a mutant form of Foxp3.

A reference for you to look at:
Waldmann, T et al. – Nature Rev Immuno 2006(8)595-601


Hope this helps

 

[teedub]

That study is correct. It turns out IL-2 has a redundant backup that is used for many, but not all, of its functions - IL-15. In summary, IL-2 and IL-15 both can regulate:
1. Proliferation/Activation of B & T cells
2. Ig Systenthesis in B-Cells
3. Induce CTLs

IL-2 ONLY functionality
1. implicated in Activated-Induced Cell Death (AICD) - Related to over active TCR response and a limit to autoreactivity
2. Required for Tregs maintance that are CD-25+ (High) which is the IL-2receptor and NEVER make their own IL-2 due to repression from foxp3.

So by knocking out IL-2 cytokine, one apparently loses a class of T-cells called tregs. This condition results in rampant/multi organ autoimmune attack against self, since Tregs suppress the activation of autoreactive Tcells. This condition is similar to IPEX (Immune dysregulation, polyendcroneopathy X-linked) syndrom, which is caused by a mutant form of Foxp3.

A reference for you to look at:
Waldmann, T et al. – Nature Rev Immuno 2006(8)595-601


Hope this helps

hey nice work....