How does the immune system distinguish between a TH1 and a TH2 response?

Question

Hello and thanks for taking the time to read my post.

I know that naive T-Cells (T0) can be induced to become mature T-Helper cells (TH1 or TH2) by induction with either IL2 or IL4.

IL2+ TH0 -> TH1 Humoral (antibody-mediated)
IL4+ TH0 -> TH2 Cell Mediated response

But what I would like to know is the causal chain that creates the IL2 and IL4 cytokines.

The reason I ask is because one clinician has reported that Azythromycin(an anti biotic) is useful in treating COVID-19(a virus) disease and was wondering if the immune system might become confused about whether should develop a TH1 or TH2 response.

If you can provide me with any help I would greatly appreciate it

Thanks in Advance Michael Mckeon

Answer 1

From what I have read, the Stage 3 differentiation depends on the surrounding cytokine environment. IL-2 does not specifically promote T-Cell differentiation, it is a general growth factor which promotes proliferation, and is secreted by both profiles.

Differentiation of T-Cell into Th1 is controlled by Interferon Gamma, the production of which is stimulated by IL-12, which is secreted by many APCs (upon stimulation by IFN Gamma produced by cells, in a self-feeding loop). IFN Gamma also suppresses IL-4 production.

Th2 cells are promoted by IL-4. It is not exactly known which cell initially produces IL-4, but it could be basophils. IL-4 then acts in a self-promoting loop, which encourages T-Cells to produce IL-4 as well as other effector cytokines, and also stimulates IL-10 production, which suppresses production of IFN Gamma and IL-12.

Thus, each pathway is self-promoting and suppresses the other pathway, ensuring that the immune response is set in stone.